SMILES stringlengths 8 687 | MIE_Results unknown | AOP_ID listlengths 1 7 | AOP_Context listlengths 1 7 | Reasoning listlengths 1 6 | Overall_Assessment dict | Answer listlengths 1 3 |
|---|---|---|---|---|---|---|
CCCCCCCC(O)(C(N)=O)c1cccc(Cl)c1 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: Inhibition of SCN5A sodium channels impairs the rapid influx of sodium ions during the depolarization phase of the cardiac action potential. This disruption slows the rate of depolarization and prolongs... | {
"Summary": "The query compound inhibits SCN5A voltage-gated sodium channels, which are critical for normal cardiac electrical function. This inhibition disrupts the action potential in cardiomyocytes, leading to altered electrical conduction and reduced cardiac contractility. The resulting impairment of cardiac out... | [
"cardiotoxicity"
] |
COc1cc(C(F)(F)F)ccc1OCC(O)CN1CCC(N2Cc3ccccc3C2=O)CC1 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The compound inhibits SCN5A (cardiac sodium channel Nav1.5), which is critical for normal cardiac action potential generation and propagation. This inhibition disrupts the depolarization phase of the cardiac action potential, leading to altered electrical conduction and reduced cardiac contractility. Th... | [
"cardiotoxicity"
] |
O=C(N[C@@H]1COc2cccc(-c3cccnc3)c2C1)c1ccc(OC(F)(F)F)cc1 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The query compound inhibits SCN5A (cardiac sodium channel Nav1.5), which is the molecular initiating event in AOP 553. This inhibition disrupts normal cardiac action potential generation and propagation, leading to altered electrical conduction and decreased myocardial contractility. The cascade of even... | [
"cardiotoxicity"
] |
O=S(=O)(Nc1nccs1)c1cc(Cl)c(NC2(c3ccccc3F)CC2)cc1F | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The query compound inhibits SCN5A (cardiac sodium channel Nav1.5), which is the molecular initiating event in AOP 553. This inhibition disrupts normal cardiac action potential generation and propagation, leading to decreased cardiac contractility. The resulting impairment of cardiac output and hemodynam... | [
"cardiotoxicity"
] |
O=S(=O)(Nc1nccs1)c1ccc2c(c1)OCCN2c1ccccc1 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The compound inhibits SCN5A (cardiac sodium channel Nav1.5), which is a critical molecular initiating event that disrupts cardiac action potential generation and propagation. This inhibition impairs sodium-dependent depolarization, leading to altered action potentials and decreased cardiac contractility... | [
"cardiotoxicity"
] |
COc1cc(-c2cc(F)cc(F)c2)c(C#N)cc1-c1nccc2cc(S(=O)(=O)Nc3ncccn3)ccc12 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The query compound inhibits SCN5A (cardiac sodium channel Nav1.5), which is the molecular initiating event in AOP 553. This inhibition disrupts normal cardiac action potential generation and propagation, leading to altered electrical conduction and decreased myocardial contractility. The cascade of even... | [
"cardiotoxicity"
] |
COc1cc(-c2cccc(F)c2)c(Cl)cc1-c1ncnc2cc(S(=O)(=O)Nc3ncccn3)ccc12 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: Inhibition of SCN5A sodium channels impairs the rapid influx of sodium ions during the depolarization phase of the cardiac action potential. This disruption slows the rate of action potential upstroke a... | {
"Summary": "The query compound inhibits SCN5A voltage-gated sodium channels, which are critical for normal cardiac electrical function. This inhibition disrupts the action potential, leading to altered cardiac conduction and decreased myocardial contractility. The sustained reduction in cardiac contractile force re... | [
"cardiotoxicity"
] |
Cc1cc(C(=O)NS(C)(=O)=O)c(F)cc1-c1cnc(N2CCC[C@H]2c2ccccc2)c(Cl)c1 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: Inhibition of SCN5A sodium channels impairs the rapid influx of sodium ions during the depolarization phase of the cardiac action potential. This disruption slows the rate of depolarization and conducti... | {
"Summary": "The query compound inhibits SCN5A voltage-gated sodium channels, which are critical for normal cardiac electrical function. This inhibition disrupts the action potential, impairs cardiac contractility, and ultimately leads to heart failure through compromised excitation-contraction coupling and reduced ... | [
"cardiotoxicity"
] |
COc1ncccc1-c1c(NC(=O)c2cccc(-c3ccccn3)c2)cccc1C(F)(F)F | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The query compound inhibits SCN5A (cardiac sodium channel Nav1.5), which is the molecular initiating event in AOP 553. This inhibition disrupts normal cardiac action potential generation and propagation, leading to decreased cardiac contractility. Sustained impairment of contractile function results in ... | [
"cardiotoxicity"
] |
COc1cc(-c2ccccc2C)c(C#N)cc1-c1nccc2cc(S(=O)(=O)Nc3ccon3)ccc12 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The query compound inhibits SCN5A (cardiac voltage-gated sodium channel Nav1.5), which is the molecular initiating event in AOP 553. This inhibition disrupts normal cardiac action potential generation and propagation, leading to altered electrical signaling in cardiomyocytes. The resulting decrease in c... | [
"cardiotoxicity"
] |
CS(=O)(=O)NC(=O)c1ccc(OCC23CC4CC(CC(C4)C2)C3)c(C2CC2)c1 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: Inhibition of SCN5A sodium channels impairs the rapid influx of sodium ions during the depolarization phase of the cardiac action potential. This disruption slows the rate of depolarization and prolongs... | {
"Summary": "The query compound inhibits SCN5A voltage-gated sodium channels, which are critical for normal cardiac action potential generation and propagation. This inhibition disrupts the depolarization phase of the cardiac action potential, leading to altered electrical signaling and decreased cardiac contractili... | [
"cardiotoxicity"
] |
CC[C@H](C)[C@@H]1NC(=O)[C@@H]2CSSC[C@@H]3NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H]4CCCN4C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CSSC[C@H](NC(=O)[C@@H](N)CC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N2)NC(=O)[C@H](CSSC[C@@H... | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The query compound, a complex cyclic peptide with multiple disulfide bonds, inhibits SCN5A (cardiac voltage-gated sodium channel Nav1.5). This inhibition disrupts normal cardiac action potential generation and propagation, leading to altered electrical conduction in the heart. The resulting decrease in ... | [
"cardiotoxicity"
] |
CC[C@H](C)[C@@H]1NC(=O)[C@@H]2CSSC[C@@H]3NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H]4CCCN4C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CSSC[C@H](NC(=O)[C@@H](N)CC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(=O)N[C@@H](Cc4ccccc4)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N2)NC(=O)[C@H](CS... | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition reduces sodium ion influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Impaired sodium chann... | {
"Summary": "The query compound, a complex cyclic peptide with multiple disulfide bonds, inhibits SCN5A (Nav1.5), the primary cardiac sodium channel. This inhibition disrupts the normal depolarization phase of cardiac action potentials, leading to altered electrical conduction and reduced cardiac contractility. The ... | [
"cardiotoxicity"
] |
Cc1onc(-c2c(Cl)cccc2Cl)c1N(C)C(=O)NCc1ccc(OC2CCOCC2)nc1 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs the rapid depolarization phase of the cardiac action potential by reducing inward sodium current, leading to altered action potential morphology and conduction velocity.",
... | {
"Summary": "The query compound inhibits SCN5A (cardiac sodium channel Nav1.5), which is the molecular initiating event in AOP 553. This inhibition disrupts the normal cardiac action potential by reducing sodium influx during depolarization. The resulting altered action potential leads to decreased cardiac contracti... | [
"cardiotoxicity"
] |
CN(C)c1cccc(-c2cn(C)c3cc(S(=O)(=O)Nc4ncns4)ccc23)c1 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The query compound inhibits SCN5A (cardiac sodium channel Nav1.5), which is a critical molecular initiating event in AOP 553. This inhibition disrupts normal cardiac action potential generation and propagation, leading to decreased cardiac contractility. The resulting impairment of cardiac output and he... | [
"cardiotoxicity"
] |
CC[C@H](C)[C@@H]1NC(=O)[C@@H]2CSSC[C@@H]3NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H]4CCCN4C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CSSC[C@H](NC(=O)[C@@H](N)CC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](Cc4ccccc4)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N2)NC(=O)[C@H](CSSC[C... | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium ion influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potent... | {
"Summary": "The query compound, a complex cyclic peptide with multiple disulfide bonds, inhibits SCN5A (cardiac sodium channel Nav1.5). This inhibition disrupts the normal depolarization phase of cardiac action potentials, leading to altered electrical conduction and action potential morphology. The resulting decre... | [
"cardiotoxicity"
] |
CC[C@H](C)[C@@H]1NC(=O)[C@@H]2CSSC[C@@H]3NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H]4CCCN4C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CSSC[C@H](NC(=O)[C@@H](N)CC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](Cc4ccccc4)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N2)NC(=O)[C@@H](CSSC[... | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition reduces sodium ion influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Impaired sodium chann... | {
"Summary": "The query compound, a complex cyclic peptide with multiple disulfide bonds, inhibits SCN5A (cardiac sodium channel Nav1.5). This inhibition disrupts the normal influx of sodium ions during cardiac action potential depolarization, leading to altered electrical conduction and action potential morphology. ... | [
"cardiotoxicity"
] |
Cc1ccc(Oc2ncc(-c3cc(F)c(C(=O)NS(C)(=O)=O)cc3Cl)cc2Cl)cc1F | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The query compound inhibits SCN5A (Nav1.5), a critical voltage-gated sodium channel essential for cardiac electrical function. This inhibition disrupts normal action potential generation and propagation in cardiomyocytes, leading to decreased cardiac contractility and ultimately heart failure. The compo... | [
"cardiotoxicity"
] |
Fc1ccc(C(CCCNCCCN2CCCCC2)c2ccc(F)cc2)cc1 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: Inhibition of SCN5A sodium channels impairs the rapid influx of sodium ions during the depolarization phase of the cardiac action potential. This disruption slows the rate of depolarization and prolongs... | {
"Summary": "The query compound inhibits SCN5A voltage-gated sodium channels, which are critical for normal cardiac action potential generation and propagation. This inhibition disrupts the depolarization phase of the cardiac action potential, leading to altered electrical conduction and decreased cardiac contractil... | [
"cardiotoxicity"
] |
CC[C@H](C)[C@@H]1NC(=O)[C@@H]2CSSC[C@@H]3NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H]4CCCN4C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CSSC[C@H](NC(=O)[C@@H](N)CC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](Cc4ccccc4)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N2)NC(=O)[C@H](CSSC[C... | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium ion influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potent... | {
"Summary": "The query compound, a complex cyclic peptide with multiple disulfide bonds, exhibits inhibition of SCN5A (cardiac voltage-gated sodium channel Nav1.5). This MIE directly impairs cardiac action potential generation and propagation, leading to decreased myocardial contractility. The mechanistic chain prog... | [
"cardiotoxicity"
] |
O=S(=O)(Nc1nccs1)c1ccc2c(c1)OCCN2c1cccc2ccncc12 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The compound inhibits SCN5A (cardiac sodium channel Nav1.5), which is the primary molecular initiating event in AOP 553. This inhibition disrupts normal cardiac action potential generation and propagation, leading to decreased cardiac contractility and ultimately heart failure. The structural features o... | [
"cardiotoxicity"
] |
COc1cc(-c2ccc(F)cc2)c(C#N)cc1-c1nccc2cc(S(=O)(=O)Nc3ccon3)ccc12 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The query compound inhibits SCN5A (cardiac voltage-gated sodium channel Nav1.5), which is the molecular initiating event in AOP 553. This inhibition disrupts normal cardiac action potential generation and propagation, leading to altered electrical signaling in cardiomyocytes. The resulting decrease in c... | [
"cardiotoxicity"
] |
COc1cc2nnc(C(F)(F)F)n2cc1-c1ccc(OC(F)(F)F)cc1 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The compound inhibits SCN5A (cardiac sodium channel Nav1.5), which is the molecular initiating event in AOP 553. This inhibition disrupts normal cardiac action potential generation and propagation, leading to altered electrical activity in the heart. The resulting decrease in cardiac contractility and c... | [
"cardiotoxicity"
] |
CC1CC(CNc2cc(F)c(S(=O)(=O)Nc3nccs3)cc2Cl)CC(C)O1 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The query compound inhibits SCN5A (cardiac voltage-gated sodium channel Nav1.5), which is the molecular initiating event in AOP 553. This inhibition disrupts normal cardiac action potential generation and propagation, leading to decreased cardiac contractility and ultimately heart failure. The compound'... | [
"cardiotoxicity"
] |
O=S(=O)(Nc1ncns1)c1cc(F)c(OCC2(F)CNCCC2c2ccc(F)cc2)cc1F | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The compound inhibits SCN5A (cardiac sodium channel Nav1.5), which is a critical molecular initiating event that disrupts cardiac action potential generation and propagation. This inhibition leads to altered electrical signaling in cardiomyocytes, resulting in decreased cardiac contractility and ultimat... | [
"cardiotoxicity"
] |
CS(=O)(=O)NC(=O)c1cc(C2CC2)c(OCC2CCN(Cc3cc(Cl)cc(Cl)c3)CC2)cc1F | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: Inhibition of SCN5A sodium channels impairs the rapid depolarization phase of the cardiac action potential, reducing the rate of sodium ion influx into cardiomyocytes during phase 0.",
"Step 2: Al... | {
"Summary": "The query compound inhibits SCN5A voltage-gated sodium channels, which are critical for cardiac action potential generation and propagation. This inhibition disrupts normal cardiac electrophysiology by impairing depolarization, altering action potential morphology, and reducing cardiac contractility. Th... | [
"cardiotoxicity"
] |
Cc1cc(C(=O)NS(C)(=O)=O)c(F)cc1-c1cnc(OCc2nc3ccccc3s2)c(Cl)c1 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The query compound inhibits SCN5A (cardiac voltage-gated sodium channel Nav1.5), which is the molecular initiating event in AOP 553. This inhibition disrupts normal cardiac action potential generation and propagation, leading to decreased cardiac contractility and ultimately heart failure. The compound'... | [
"cardiotoxicity"
] |
COc1cc(-c2ccc(C)c(F)c2)c(C#N)cc1-c1nccc2cc(S(=O)(=O)Nc3ccon3)ccc12 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The query compound inhibits SCN5A (cardiac sodium channel Nav1.5), which is a critical molecular initiating event in AOP 553. This inhibition disrupts normal cardiac action potential generation and propagation, leading to decreased cardiac contractility. The resulting reduction in cardiac output and hem... | [
"cardiotoxicity"
] |
COc1ccc2c(c1)NC1(CCN(C(=O)c3ccc4c(c3)N(C)CCO4)CC1)c1cccn1-2 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: Inhibition of SCN5A sodium channels impairs the rapid depolarization phase of the cardiac action potential, reducing the rate of sodium ion influx into cardiomyocytes.",
"Step 2: Altered action po... | {
"Summary": "The compound inhibits SCN5A voltage-gated sodium channels, which are critical for cardiac action potential generation and propagation. This inhibition disrupts normal cardiac electrophysiology by impairing sodium influx during depolarization, leading to altered action potentials with reduced conduction ... | [
"cardiotoxicity"
] |
O=S(=O)(Nc1nccs1)c1ccc2c(c1)OCCN2c1cccc(OC(F)F)c1 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The query compound inhibits SCN5A (cardiac sodium channel Nav1.5), which is the molecular initiating event in AOP 553. This inhibition disrupts cardiac action potential generation and propagation, leading to altered electrical conduction, decreased myocardial contractility, and ultimately heart failure.... | [
"cardiotoxicity"
] |
C[C@H](Nc1cc(F)c(S(=O)(=O)Nc2nccs2)c(F)c1)c1ccccc1F | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: Inhibition of SCN5A sodium channels impairs the rapid influx of sodium ions during the depolarization phase of the cardiac action potential. This disruption slows the rate of depolarization and prolongs... | {
"Summary": "The query compound inhibits SCN5A (Nav1.5), a critical voltage-gated sodium channel essential for cardiac action potential generation and propagation. This inhibition disrupts normal cardiac electrophysiology by impairing sodium-dependent depolarization, leading to altered action potentials and decrease... | [
"cardiotoxicity"
] |
COCCNc1cc(C(F)(F)F)ccc1N1CCOc2cc(S(=O)(=O)Nc3ccncn3)ccc21 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The query compound inhibits SCN5A (cardiac sodium channel Nav1.5), which is the molecular initiating event in AOP 553. This inhibition disrupts normal cardiac action potential generation and propagation, leading to altered electrical activity in the heart. The resulting decrease in cardiac contractility... | [
"cardiotoxicity"
] |
COc1ccc2c(c1)NC1(CCN(C(=O)c3cccc(Cl)c3)CC1)c1cccn1-2 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: Inhibition of SCN5A sodium channels impairs the rapid influx of sodium ions during the depolarization phase of cardiac action potentials. This disruption slows the rate of depolarization and conduction ... | {
"Summary": "The query compound inhibits SCN5A voltage-gated sodium channels, a critical molecular initiating event that disrupts cardiac action potential generation and propagation. This inhibition impairs the rapid depolarization phase necessary for normal cardiac electrical function, leading to altered action pot... | [
"cardiotoxicity"
] |
C[C@H](Nc1cc(F)c(S(=O)(=O)Nc2ncc(Cl)s2)cc1Cl)c1ccccc1F | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The compound inhibits SCN5A (cardiac sodium channel Nav1.5), which is the molecular initiating event in AOP 553. This inhibition disrupts normal cardiac action potential generation and propagation, leading to altered electrical activity in the heart. The resulting decrease in cardiac contractility and h... | [
"cardiotoxicity"
] |
N#Cc1cc(C(F)(F)F)ccc1N1CCOc2cc(S(=O)(=O)Nc3ncco3)ccc21 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The query compound inhibits SCN5A (cardiac voltage-gated sodium channel Nav1.5), which is the molecular initiating event in AOP 553. This inhibition disrupts normal cardiac action potential generation and propagation, leading to altered electrical signaling in cardiomyocytes. The resulting decrease in c... | [
"cardiotoxicity"
] |
Cc1noc(C)c1-c1cn(C)c2cc(S(=O)(=O)Nc3ncns3)ccc12 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The compound inhibits SCN5A (cardiac sodium channel Nav1.5), which is critical for normal cardiac action potential generation and propagation. This inhibition disrupts the depolarization phase of the cardiac action potential, leading to altered electrical conduction and reduced cardiac contractility. Th... | [
"cardiotoxicity"
] |
COc1cc(-c2nnc(S(=O)(=O)C3CCC3)[nH]2)c(F)cc1-c1cnc(OCC(C)C)c(Cl)c1 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: Inhibition of SCN5A reduces sodium ion influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Impaired sodium ch... | {
"Summary": "The query compound inhibits SCN5A (Nav1.5), a critical voltage-gated sodium channel essential for cardiac electrical function. This inhibition disrupts normal action potential generation and propagation in cardiomyocytes, leading to altered cardiac electrophysiology. The resulting impairment of action p... | [
"cardiotoxicity"
] |
CC[C@H](Oc1cc(F)c(S(=O)(=O)Nc2cscn2)cc1Cl)c1ccccc1F | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: Inhibition of SCN5A reduces sodium ion influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Impaired sodium ch... | {
"Summary": "The compound inhibits SCN5A (cardiac sodium channel Nav1.5), a critical molecular initiating event that disrupts cardiac electrophysiology. This inhibition impairs sodium-dependent depolarization, leading to altered action potentials with reduced conduction velocity. The electromechanical uncoupling res... | [
"cardiotoxicity"
] |
C[C@H](Nc1cc(F)c(S(=O)(=O)Nc2nccs2)cc1Cl)c1cc(Cl)ccc1F | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The compound inhibits SCN5A (cardiac sodium channel Nav1.5), which is a critical molecular initiating event that disrupts cardiac action potential generation and propagation. This inhibition impairs sodium-dependent depolarization, leading to altered electrical conduction and reduced cardiac contractili... | [
"cardiotoxicity"
] |
[N-]=[N+]=Nc1ccc(N2CCOc3cc(S(=O)(=O)Nc4nccs4)ccc32)c(C2=CCNCC2)c1 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: Inhibition of SCN5A sodium channels impairs the rapid depolarization phase of the cardiac action potential, reducing the rate of sodium ion influx into cardiomyocytes.",
"Step 2: Altered action po... | {
"Summary": "The query compound inhibits SCN5A voltage-gated sodium channels, which are critical for normal cardiac action potential generation and propagation. This inhibition disrupts the rapid depolarization phase necessary for efficient electrical conduction in the heart, leading to altered action potentials and... | [
"cardiotoxicity"
] |
O=C1c2nc(-c3ccc(OC(F)(F)F)cc3)ccc2OCCN1Cc1ccccc1 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The query compound inhibits SCN5A (cardiac sodium channel Nav1.5), which is the molecular initiating event in AOP 553. This inhibition disrupts normal cardiac action potential generation and propagation, leading to altered electrical conduction, decreased cardiac contractility, and ultimately heart fail... | [
"cardiotoxicity"
] |
O=S(=O)(Nc1cscn1)c1cc(Cl)c(NCc2cc(CCN3CC(F)C3)ccc2F)cc1F | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The query compound inhibits SCN5A (cardiac sodium channel Nav1.5), which is the molecular initiating event in AOP 553. This inhibition disrupts normal cardiac action potential generation and propagation, leading to decreased cardiac contractility through impaired excitation-contraction coupling. The res... | [
"cardiotoxicity"
] |
O=C(O)CCCC1(c2ccccc2)CCCN(C(=O)Nc2ccc(Cl)cc2)C1 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium ion influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potent... | {
"Summary": "The query compound inhibits SCN5A (cardiac sodium channel Nav1.5), which is the molecular initiating event in AOP 553. This inhibition disrupts normal cardiac action potential generation and propagation, leading to altered electrical activity in cardiomyocytes. The resulting impairment of sodium-depende... | [
"cardiotoxicity"
] |
Cc1cc(C(=O)NS(=O)(=O)c2nccs2)c(F)cc1-c1cnc(Oc2c(C)cc(Cl)cc2Cl)c(Cl)c1 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The query compound inhibits SCN5A (Nav1.5), a critical voltage-gated sodium channel essential for cardiac action potential generation and propagation. This inhibition disrupts normal cardiac electrophysiology by impairing sodium-dependent depolarization, leading to altered action potentials and decrease... | [
"cardiotoxicity"
] |
CS(=O)(=O)NC(=O)c1cc(Cl)c(OCC2CC3C4CCC(C4)C3C2)cc1F | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: Inhibition of SCN5A reduces sodium ion influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Impaired sodium ch... | {
"Summary": "The compound inhibits SCN5A (voltage-gated sodium channel Nav1.5), a critical regulator of cardiac electrical activity. This inhibition disrupts normal action potential generation and propagation in cardiomyocytes, leading to altered electrical conduction patterns. The resulting impairment of excitation... | [
"cardiotoxicity"
] |
COc1cc(-c2cc(F)cnc2OC)ccc1-c1ccnc2cc(S(=O)(=O)Nc3nncs3)ccc12 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The query compound inhibits SCN5A (cardiac sodium channel Nav1.5), which is the molecular initiating event in AOP 553. This inhibition disrupts normal cardiac action potential generation and propagation, leading to altered electrical signaling in the heart. The resulting decrease in cardiac contractilit... | [
"cardiotoxicity"
] |
COc1ncc(-c2c(C)ccc(F)c2CCNC(=O)c2ccc(OCCC(F)(F)F)nc2)cn1 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The query compound inhibits SCN5A (cardiac sodium channel Nav1.5), which is the molecular initiating event in AOP 553. This inhibition disrupts normal cardiac action potential generation and propagation, leading to decreased cardiac contractility. Sustained impairment of contractile function progresses ... | [
"cardiotoxicity"
] |
CC[C@H](C)[C@@H]1NC(=O)[C@@H]2CSSC[C@@H]3NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H]4CCCN4C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CSSC[C@H](NC(=O)[C@@H](N)CC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](Cc4ccccc4)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N2)NC(=O)[C@H](CS... | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The query compound is a complex cyclic peptide with multiple disulfide bonds that inhibits SCN5A (cardiac voltage-gated sodium channel Nav1.5). This inhibition disrupts normal cardiac action potential generation and propagation, leading to decreased cardiac contractility through impaired excitation-cont... | [
"cardiotoxicity"
] |
O=C(Nc1ccc(Cl)cc1)N1CCCC(CCCO)(c2ccccc2)C1 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The compound inhibits SCN5A (cardiac sodium channel Nav1.5), which is the molecular initiating event in AOP 553. This inhibition disrupts normal cardiac action potential generation and propagation, leading to altered electrical conduction and decreased myocardial contractility. The resulting reduction i... | [
"cardiotoxicity"
] |
CN(C)c1noc2ccc(C3NCCOC3Oc3cc(F)c(S(=O)(=O)Nc4ncns4)cc3F)cc12 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: Inhibition of SCN5A sodium channels impairs the rapid influx of sodium ions during the depolarization phase of the cardiac action potential. This disruption slows the rate of action potential upstroke a... | {
"Summary": "The query compound inhibits SCN5A voltage-gated sodium channels, which are critical for normal cardiac electrical function. This inhibition disrupts the action potential upstroke, leading to altered cardiac conduction and reduced myocardial contractility. The sustained decrease in cardiac contractile fo... | [
"cardiotoxicity"
] |
CCN(CC)C(=O)CCC1(c2ccccc2)CCCN(C(=O)Nc2ccc(Cl)cc2)C1 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The compound inhibits SCN5A (cardiac sodium channel Nav1.5), which is the molecular initiating event in AOP 553. This inhibition disrupts normal cardiac action potential generation and propagation, leading to altered electrical activity in cardiomyocytes. The resulting decrease in cardiac contractility ... | [
"cardiotoxicity"
] |
CN(Cc1cccc(F)c1CNc1ncc(S(=O)(=O)Nc2cscn2)cc1Cl)C(C)(C)C | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The compound inhibits SCN5A (cardiac sodium channel Nav1.5), which is a critical molecular initiating event that disrupts cardiac action potential generation and propagation. This inhibition leads to altered electrical activity in cardiomyocytes, decreased cardiac contractility, and ultimately heart fai... | [
"cardiotoxicity"
] |
O=S(=O)(Nc1nccs1)c1cc(Cl)c(NC(c2ccccc2)C2CC2)cc1F | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The query compound inhibits SCN5A (cardiac voltage-gated sodium channel Nav1.5), which is the molecular initiating event in AOP 553. This inhibition disrupts normal cardiac action potential generation and propagation, leading to altered electrical signaling in cardiomyocytes. The resulting decrease in c... | [
"cardiotoxicity"
] |
CC[C@H](C)[C@@H]1NC(=O)[C@@H]2CSSC[C@@H]3NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H]4CCCN4C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CSSC[C@H](NC(=O)[C@@H](N)CC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc4c[nH]c5ccccc45)C(=O)N[C@@H](Cc4ccccc4)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(... | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition reduces sodium ion influx during the depolarization phase of cardiac action potentials, disrupting normal electrolyte balance in cardiomyocytes.",
"Step 2: Impaired sodium influx ... | {
"Summary": "The query compound, a complex cyclic peptide with multiple disulfide bonds, inhibits SCN5A (Nav1.5), the primary cardiac sodium channel. This inhibition disrupts the normal cardiac action potential by reducing sodium influx during depolarization, leading to altered electrical conduction and decreased my... | [
"cardiotoxicity"
] |
O=S(=O)(Nc1ncns1)N1CCc2c(cccc2-c2ccc(C(F)(F)F)cc2-c2cccnc2)C1 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting the normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potent... | {
"Summary": "The query compound inhibits SCN5A (cardiac sodium channel Nav1.5), which is the molecular initiating event in AOP 553. This inhibition disrupts normal cardiac action potential generation and propagation, leading to altered electrical conduction, decreased myocardial contractility, and progression to hea... | [
"cardiotoxicity"
] |
O=C(NS(=O)(=O)C1COC1)c1cc(C2CC2)c(OCC23CC4CC(CC(C4)C2)C3)cc1F | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The query compound inhibits SCN5A (Nav1.5), a critical voltage-gated sodium channel essential for cardiac action potential generation and propagation. This inhibition disrupts normal cardiac electrophysiology by impairing sodium influx during depolarization, leading to altered action potentials and redu... | [
"cardiotoxicity"
] |
N#Cc1cc(C(F)(F)F)ccc1N1CCOc2cc(S(=O)(=O)Nc3nccs3)c(F)cc21 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The query compound inhibits SCN5A (cardiac voltage-gated sodium channel Nav1.5), which is the molecular initiating event in AOP 553. This inhibition disrupts normal cardiac action potential generation and propagation, leading to altered electrical conduction and decreased myocardial contractility. The r... | [
"cardiotoxicity"
] |
CCc1cccc(SC[C@@H](C)CN[C@@H]2COc3ccccc3SC2)c1O | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The compound inhibits SCN5A (cardiac sodium channel Nav1.5), a critical ion channel for cardiac action potential generation and propagation. This inhibition disrupts normal cardiac electrophysiology by reducing sodium influx during depolarization, leading to altered action potentials and decreased cardi... | [
"cardiotoxicity"
] |
O=S(=O)(Nc1ncns1)N1CCc2c(cccc2-c2ccc(C(F)(F)F)cc2N2CCOCC2)C1 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs the rapid depolarization phase of the cardiac action potential by reducing inward sodium current, leading to slowed conduction velocity and prolonged action potential duration i... | {
"Summary": "The query compound inhibits SCN5A (cardiac sodium channel Nav1.5), which is the molecular initiating event in AOP 553. This inhibition disrupts the normal cardiac action potential by reducing sodium influx during depolarization, leading to altered electrical conduction and decreased cardiac contractilit... | [
"cardiotoxicity"
] |
O=S(=O)(Nc1nccs1)c1ccc2c(c1)OCCN2c1ccc(Cl)c(Cl)c1 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The compound inhibits SCN5A (cardiac sodium channel Nav1.5), which is the molecular initiating event in AOP 553. This inhibition disrupts normal cardiac action potential generation and propagation, leading to altered electrical activity in the heart. The resulting decrease in cardiac contractility impai... | [
"cardiotoxicity"
] |
Cc1ccc([C@H]2CCNC[C@@H]2COc2cc(F)c(S(=O)(=O)Nc3ncns3)cc2F)cc1 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The query compound inhibits SCN5A (cardiac sodium channel Nav1.5), a critical molecular initiating event that disrupts cardiac action potential generation and propagation. This inhibition impairs sodium-dependent depolarization, leading to altered electrical activity and compromised excitation-contracti... | [
"cardiotoxicity"
] |
Cc1ccc(C2CCNC[C@H]2COc2cc(F)c(S(=O)(=O)Nc3ncns3)cc2F)cc1 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs the rapid depolarization phase of the cardiac action potential by reducing inward sodium current, leading to slowed conduction velocity and prolonged action potential duration."... | {
"Summary": "The query compound inhibits SCN5A (cardiac sodium channel Nav1.5), which is the molecular initiating event in AOP 553. This inhibition disrupts normal cardiac action potential generation and propagation, leading to decreased cardiac contractility and progression to heart failure. The compound's structur... | [
"cardiotoxicity"
] |
COc1cnc(-c2c(C)ccc(F)c2CCNC(=O)c2ccc(COCC(F)(F)F)nc2)cn1 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium ion influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potent... | {
"Summary": "The query compound inhibits SCN5A (cardiac voltage-gated sodium channel Nav1.5), which is the molecular initiating event in AOP 553. This inhibition disrupts normal cardiac action potential generation and propagation, leading to altered electrical activity in cardiomyocytes. The resulting decrease in ca... | [
"cardiotoxicity"
] |
O=S(=O)(Nc1cccc(F)n1)c1cc(F)c(O[C@H]2CCN(CC(F)(F)F)C[C@@H]2c2ccc(F)c(F)c2)cc1F | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: Inhibition of SCN5A reduces sodium ion influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Impaired sodium ch... | {
"Summary": "The query compound inhibits SCN5A (cardiac sodium channel Nav1.5), which is the molecular initiating event in AOP 553. This inhibition disrupts normal cardiac action potential generation and propagation, leading to altered electrical activity in the heart. The resulting impairment of action potential dy... | [
"cardiotoxicity"
] |
O=S(=O)(Nc1cccc(F)n1)c1cc(F)c(OC2CCN(CC(F)(F)F)CC2c2ccc(F)c(F)c2)cc1F | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium ion influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Reduced sodium conduc... | {
"Summary": "The query compound inhibits SCN5A (cardiac sodium channel Nav1.5), which is the molecular initiating event in AOP 553. This inhibition disrupts normal cardiac action potential generation and propagation, leading to decreased cardiac contractility through impaired excitation-contraction coupling. The sus... | [
"cardiotoxicity"
] |
COc1ccc2c(c1)NC1(CCN(C(=O)c3cc(C)cc(C)c3)CC1)c1cccn1-2 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The compound inhibits SCN5A (cardiac sodium channel Nav1.5), which is critical for normal cardiac action potential generation and propagation. This inhibition disrupts the depolarization phase of the cardiac action potential, leading to altered electrical conduction and reduced cardiac contractility. Th... | [
"cardiotoxicity"
] |
Cn1cc(-c2ccc(C(F)F)cc2)c2cc(F)c(C(=O)NS(=O)(=O)C3CC3)cc21 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The query compound inhibits SCN5A (cardiac sodium channel Nav1.5), which is the molecular initiating event in AOP 553. This inhibition disrupts normal cardiac action potential generation and propagation, leading to altered electrical signaling in cardiomyocytes. The resulting decrease in cardiac contrac... | [
"cardiotoxicity"
] |
CC[C@H](C)[C@@H]1NC(=O)[C@@H]2CSSC[C@@H]3NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H]4CCCN4C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CSSC[C@H](NC(=O)[C@@H](N)CC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](Cc4ccccc4)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N2)NC(=O)[C@H](CSSC[C... | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The query compound, a complex cyclic peptide with multiple disulfide bonds, inhibits SCN5A (Nav1.5), the primary cardiac sodium channel. This inhibition disrupts normal cardiac action potential generation and propagation, leading to decreased myocardial contractility. The resulting reduction in cardiac ... | [
"cardiotoxicity"
] |
Fc1ccccc1Cn1ccc2c(OC3CCN(Cc4ccccn4)CC3)ncnc21 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The compound inhibits SCN5A (cardiac voltage-gated sodium channel Nav1.5), which is a critical molecular initiating event leading to cardiotoxicity. This inhibition disrupts normal cardiac action potential generation and propagation, resulting in decreased cardiac contractility and ultimately heart fail... | [
"cardiotoxicity"
] |
Cc1cc(C(=O)NS(C)(=O)=O)c(F)cc1-c1cnc(N2CCC[C@@H]2c2ccc(Cl)c(Cl)c2)c(Cl)c1 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs the rapid depolarization phase of the cardiac action potential by reducing inward sodium current, leading to altered action potential morphology and conduction velocity.",
... | {
"Summary": "The query compound inhibits SCN5A (cardiac sodium channel Nav1.5), which is the molecular initiating event in AOP 553. This inhibition disrupts the normal cardiac action potential by reducing sodium influx during depolarization. The resulting altered action potential leads to decreased cardiac contracti... | [
"cardiotoxicity"
] |
O=S(=O)(Nc1nccs1)c1cc(Cl)c(NC2CCCc3ccncc32)cc1F | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The compound inhibits SCN5A (cardiac sodium channel Nav1.5), which is critical for normal cardiac action potential generation and propagation. This inhibition disrupts the depolarization phase of the cardiac action potential, leading to altered electrical conduction and reduced cardiac contractility. Th... | [
"cardiotoxicity"
] |
O=S(=O)(Nc1ncns1)c1ccc2c(c1)OCCN2c1ccccc1 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The compound inhibits SCN5A (cardiac sodium channel Nav1.5), which is critical for normal cardiac action potential generation and propagation. This inhibition disrupts the depolarization phase of the cardiac action potential, leading to altered electrical conduction and reduced cardiac contractility. Th... | [
"cardiotoxicity"
] |
Cc1cc(-c2cccc3c2C[C@H](NC(=O)c2ccc(OCCOCC(F)(F)F)nc2)CO3)cnc1CO | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The query compound inhibits SCN5A (cardiac sodium channel Nav1.5), which is the molecular initiating event in AOP 553. This inhibition disrupts normal cardiac action potential generation and propagation, leading to altered electrical activity in the heart. The resulting decrease in cardiac contractility... | [
"cardiotoxicity"
] |
CN(C)S(=O)(=O)NC(=O)c1cc(Cl)c(OCC23CC4CC(CC(C4)C2)C3)cc1F | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: Inhibition of SCN5A reduces sodium ion influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Impaired sodium ch... | {
"Summary": "The query compound inhibits SCN5A (cardiac sodium channel Nav1.5), which is the molecular initiating event in AOP 553. This inhibition disrupts normal cardiac action potential generation and propagation, leading to altered electrical activity in cardiomyocytes. The resulting impairment of action potenti... | [
"cardiotoxicity"
] |
C[C@@H]1COc2cc(S(=O)(=O)Nc3nccs3)ccc2N1c1ccc(C(F)(F)F)cc1C#N | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs the rapid inward sodium current during the depolarization phase of the cardiac action potential, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Alte... | {
"Summary": "The compound inhibits SCN5A (cardiac sodium channel Nav1.5), a critical ion channel for cardiac action potential generation and propagation. This inhibition disrupts normal cardiac electrophysiology by impairing sodium influx during depolarization, leading to altered action potentials with conduction ab... | [
"cardiotoxicity"
] |
C[C@H]1COc2cc(S(=O)(=O)Nc3nccs3)ccc2N1c1ccc(C(F)(F)F)cc1C#N | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs the rapid depolarization phase of the cardiac action potential by reducing inward sodium current, leading to slowed conduction velocity and prolonged action potential duration i... | {
"Summary": "The query compound inhibits SCN5A (cardiac sodium channel Nav1.5), which is the molecular initiating event in AOP 553. This inhibition disrupts normal cardiac action potential generation and propagation, leading to altered electrical activity in cardiomyocytes. The resulting decrease in cardiac contract... | [
"cardiotoxicity"
] |
CC1COc2cc(S(=O)(=O)Nc3nccs3)ccc2N1c1ccc(C(F)(F)F)cc1C#N | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition reduces sodium ion influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Impaired sodium chann... | {
"Summary": "The query compound inhibits SCN5A (cardiac sodium channel Nav1.5), which is the molecular initiating event in AOP 553. This inhibition disrupts normal cardiac action potential generation and propagation, leading to altered electrical activity in cardiomyocytes. The resulting impairment of excitation-con... | [
"cardiotoxicity"
] |
O=S(=O)(Nc1ncns1)N1CCc2c(cccc2-c2cccc3[nH]ncc23)C1 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The query compound inhibits SCN5A (cardiac sodium channel Nav1.5), which is the molecular initiating event in AOP 553. This inhibition disrupts normal cardiac action potential generation and propagation, leading to altered electrical signaling in the heart. The resulting decrease in cardiac contractilit... | [
"cardiotoxicity"
] |
CSCC[C@@H]1NC(=O)[C@H](Cc2ccccc2)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H](N)CC(=O)O)CSSC[C@@H]2NC(=O)[C@@H]3CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc4ccc(O)cc4)C(=O)N[C@H](C(=O)N[C@@H](Cc4ccccc4)C(N)=O)C(C)C)NC(=O)[C@H](Cc4c[nH]c5ccccc45)NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc4cnc[nH]4)NC(=O)[C@H]([C@@H](C)O)NC... | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The query compound, a complex peptide-like molecule with multiple amino acid residues and disulfide bonds, demonstrates inhibition of SCN5A (cardiac voltage-gated sodium channel Nav1.5). This MIE directly impairs cardiac action potential generation and propagation, leading to decreased myocardial contra... | [
"cardiotoxicity"
] |
COc1cc(-c2cc(OC)c(-n3c(=O)ccc4cc(S(=O)(=O)Nc5ncccn5)ccc43)cc2F)ccc1Cl | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium ion influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potent... | {
"Summary": "The query compound inhibits SCN5A (Nav1.5), a critical voltage-gated sodium channel essential for cardiac action potential generation and propagation. This inhibition disrupts normal cardiac electrophysiology by impairing sodium-dependent depolarization, leading to altered action potentials with reduced... | [
"cardiotoxicity"
] |
O=S(=O)(Nc1nccs1)c1ccc2c(c1)OCCN2c1ccccc1C(F)(F)F | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The query compound inhibits SCN5A (cardiac voltage-gated sodium channel Nav1.5), which is the molecular initiating event in AOP 553. This inhibition disrupts normal cardiac action potential generation and propagation, leading to decreased cardiac contractility and ultimately heart failure. The structura... | [
"cardiotoxicity"
] |
Cn1nccc1-c1cc(Cl)ccc1-n1cnc2cc(S(=O)(=O)Nc3ncns3)ccc21 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium ion influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potent... | {
"Summary": "The query compound inhibits SCN5A (cardiac sodium channel Nav1.5), which is the molecular initiating event in AOP 553. This inhibition disrupts normal cardiac action potential generation and propagation, leading to altered electrical signaling in the heart. The resulting decrease in cardiac contractilit... | [
"cardiotoxicity"
] |
O=S(=O)(Nc1ncns1)c1ccc2c(c1)OCCN2c1cccc2ncccc12 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The compound inhibits SCN5A (cardiac sodium channel Nav1.5), which is critical for normal cardiac action potential generation and propagation. This inhibition disrupts the depolarization phase of the cardiac action potential, leading to altered electrical conduction and reduced cardiac contractility. Th... | [
"cardiotoxicity"
] |
COc1cc(-c2cc(F)cc(F)c2)ccc1-c1nccc2cc(S(=O)(=O)Nc3ncccn3)ccc12 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs the rapid depolarization phase of the cardiac action potential by reducing sodium influx into cardiomyocytes, leading to altered action potential morphology and conduction veloc... | {
"Summary": "The query compound inhibits SCN5A (Nav1.5), a critical voltage-gated sodium channel essential for cardiac action potential generation and propagation. This inhibition disrupts normal cardiac electrophysiology by impairing sodium-dependent depolarization, leading to altered action potentials and reduced ... | [
"cardiotoxicity"
] |
CC[C@H](C)[C@@H]1NC(=O)[C@@H]2CSSC[C@@H]3NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H]4CCCN4C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CSSC[C@H](NC(=O)[C@@H](N)CC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](Cc4ccccc4)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N2)NC(=O)[C@H](CSSC[C... | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium ion influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Reduced sodium conduc... | {
"Summary": "The query compound, a complex cyclic peptide with multiple disulfide bonds, inhibits SCN5A (Nav1.5), the primary cardiac sodium channel. This inhibition disrupts normal cardiac action potential generation and propagation, leading to altered electrical conduction, decreased myocardial contractility, and ... | [
"cardiotoxicity"
] |
COc1ccc([C@H]2OC(=O)N[C@@H]2C)cc1-c1ccc(C(F)(F)F)cc1[C@@H]1CC[C@H]2[C@@H](c3cc(C(F)(F)F)cc(C(F)(F)F)c3)OC(=O)N12 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs the rapid depolarization phase of the cardiac action potential by reducing inward sodium current, leading to slowed conduction velocity and prolonged action potential duration."... | {
"Summary": "The compound inhibits SCN5A (cardiac sodium channel Nav1.5), which is a critical molecular initiating event that disrupts the normal cardiac action potential. This inhibition impairs sodium-dependent depolarization, leading to altered electrical conduction and reduced myocardial contractility. The mecha... | [
"cardiotoxicity"
] |
O=C(COc1cccc2cccnc12)Nc1ccccc1N1CCOCC1 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium ion influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potent... | {
"Summary": "The query compound inhibits SCN5A (Nav1.5), a critical voltage-gated sodium channel essential for cardiac electrical function. This inhibition disrupts normal action potential generation and propagation in cardiomyocytes, leading to altered cardiac electrophysiology. The resulting decrease in cardiac co... | [
"cardiotoxicity"
] |
CC(C)COc1ncc(-c2cn(C(C)C)c3cc(C(=O)NS(C)(=O)=O)ccc23)cc1Cl | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The query compound inhibits SCN5A (cardiac voltage-gated sodium channel Nav1.5), which is the molecular initiating event in AOP 553. This inhibition disrupts normal cardiac action potential generation and propagation, leading to altered electrical signaling in cardiomyocytes. The downstream consequence ... | [
"cardiotoxicity"
] |
O=S(=O)(Nc1nccs1)c1cc(Cl)c(NC2CCCOC2)cc1F | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The compound inhibits SCN5A (cardiac sodium channel Nav1.5), which is the molecular initiating event in AOP 553. This inhibition disrupts normal cardiac action potential generation and propagation, leading to decreased cardiac contractility. The resulting impaired cardiac output and systemic hemodynamic... | [
"cardiotoxicity"
] |
CC[C@H](C)[C@@H]1NC(=O)[C@@H]2CSSC[C@@H]3NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H]4CCCN4C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CSSC[C@H](NC(=O)[C@@H](N)CC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](Cc4ccccc4)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N2)NC(=O)[C@@H](CSSC[... | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition reduces sodium ion influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Impaired sodium chann... | {
"Summary": "The query compound, a complex cyclic peptide with multiple disulfide bonds, inhibits SCN5A (cardiac sodium channel Nav1.5). This inhibition disrupts the normal depolarization phase of cardiac action potentials, leading to altered electrical conduction and reduced cardiac contractility. The mechanistic c... | [
"cardiotoxicity"
] |
O=S(=O)(Nc1ncns1)N1CCc2c(cccc2-c2ccc(Cl)cc2)C1 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The query compound inhibits SCN5A (cardiac sodium channel Nav1.5), which is the molecular initiating event in AOP 553. This inhibition disrupts normal cardiac action potential generation and propagation, leading to altered electrical signaling in the heart. The resulting decrease in cardiac contractilit... | [
"cardiotoxicity"
] |
Cc1ccc(C(=O)NC(=N)NCCCCc2ccccc2)cc1 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: Inhibition of SCN5A sodium channels impairs the rapid influx of sodium ions during the depolarization phase of cardiac action potentials. This disruption slows the rate of action potential upstroke and ... | {
"Summary": "The query compound inhibits SCN5A voltage-gated sodium channels, which are critical for normal cardiac electrical function. This inhibition disrupts action potential generation and propagation in cardiac tissue, leading to decreased myocardial contractility and ultimately heart failure. The compound's s... | [
"cardiotoxicity"
] |
C[C@H](Nc1cc(F)c(S(=O)(=O)Nc2cscn2)c(F)c1)c1cc(Cl)ccc1F | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The query compound inhibits SCN5A (cardiac sodium channel Nav1.5), which is the molecular initiating event in AOP 553. This inhibition disrupts normal cardiac action potential generation and propagation, leading to altered electrical activity in the heart. The resulting impairment of excitation-contract... | [
"cardiotoxicity"
] |
COc1cc(C2CC2)ccc1-c1nccc2c1CCN(S(=O)(=O)Nc1ncns1)C2 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The compound inhibits SCN5A (cardiac voltage-gated sodium channel Nav1.5), which is the molecular initiating event in AOP 553. This inhibition disrupts normal cardiac action potential generation and propagation, leading to altered electrical conduction, decreased myocardial contractility, and ultimately... | [
"cardiotoxicity"
] |
O=S(=O)(Nc1nccs1)c1ccc2c(c1)OCCN2c1ccc(Cl)cc1F | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs the rapid depolarization phase of cardiac action potentials, as sodium influx through Nav1.5 is essential for the upstroke of ventricular and atrial action potentials.",
"... | {
"Summary": "The query compound inhibits SCN5A (cardiac voltage-gated sodium channel Nav1.5), which is the primary mechanism initiating AOP 553. This inhibition disrupts normal cardiac action potential generation and propagation, leading to altered electrophysiology, decreased myocardial contractility, and ultimatel... | [
"cardiotoxicity"
] |
O=c1n(Cc2nnc(C3CC3)o2)nc2ccc(-c3ccc(Oc4ccc(F)cc4)cc3)cn12 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The query compound inhibits SCN5A (cardiac sodium channel Nav1.5), which is the molecular initiating event for AOP 553. This inhibition disrupts normal cardiac action potential generation and propagation, leading to altered electrical activity in the heart. The resulting decrease in cardiac contractilit... | [
"cardiotoxicity"
] |
O=S(=O)(Nc1nccs1)c1cc(Cl)c(NCc2cccc3ccncc23)cc1F | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The query compound inhibits SCN5A (cardiac voltage-gated sodium channel Nav1.5), which is the molecular initiating event in AOP 553. This inhibition disrupts normal cardiac action potential generation and propagation, leading to altered electrical signaling in the heart. The downstream consequence is de... | [
"cardiotoxicity"
] |
CCS(=O)(=O)NC(=O)c1cc(C)c(-c2cnc(Oc3c(C)cc(Cl)cc3Cl)c(Cl)c2)cc1F | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: Inhibition of SCN5A sodium channels impairs the influx of sodium ions during the depolarization phase of the cardiac action potential, disrupting normal electrical conduction in cardiomyocytes.",
... | {
"Summary": "The query compound inhibits SCN5A voltage-gated sodium channels, which are critical for cardiac action potential generation and propagation. This inhibition disrupts normal cardiac electrical function, leading to altered action potentials, decreased myocardial contractility, and ultimately heart failure... | [
"cardiotoxicity"
] |
O=S(=O)(Nc1ncns1)N1CCc2c(cccc2-c2cccc3c2CCNC3)C1 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: SCN5A inhibition impairs sodium influx during the depolarization phase of cardiac action potentials, disrupting normal electrical conduction in cardiomyocytes.",
"Step 2: Altered action potential ... | {
"Summary": "The query compound inhibits SCN5A (Nav1.5), a critical voltage-gated sodium channel essential for cardiac electrical function. This inhibition disrupts normal action potential generation and propagation in cardiomyocytes, leading to altered cardiac electrophysiology. The resulting decrease in cardiac co... | [
"cardiotoxicity"
] |
Cc1ccc(C(=O)NC(=N)NCCCc2ccccc2)cc1 | {
"SCN5A": "Inhibition"
} | [
"Aop:553"
] | [
"\nAop:553\nTitle: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure\nAOP: Inhibition, sodium channel --> Altered, Action Potential --> Decrease, Cardiac contractility --> Heart failure\n"
] | [
{
"MIE": "Inhibition of SCN5A (Voltage-gated sodium channel Nav1.5)",
"Reasoning_Steps": [
"Step 1: Inhibition of SCN5A sodium channels impairs the rapid influx of sodium ions during the depolarization phase of the cardiac action potential. This disruption slows the rate of depolarization and prolongs... | {
"Summary": "The query compound inhibits SCN5A voltage-gated sodium channels, which are critical for normal cardiac action potential generation and propagation. This inhibition disrupts the depolarization phase of the cardiac action potential, leading to altered electrical conduction and reduced cardiac contractilit... | [
"cardiotoxicity"
] |
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