Repositioning Candidate Details
| Candidate ID: | R0099 |
| Source ID: | DB00270 |
| Source Type: | approved; investigational |
| Compound Type: | small molecule |
| Compound Name: | Isradipine |
| Synonyms: | Isradipine |
| Molecular Formula: | C19H21N3O5 |
| SMILES: | COC(=O)C1=C(C)NC(C)=C(C1C1=CC=CC2=NON=C12)C(=O)OC(C)C |
| Structure: |
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| DrugBank Description: | Isradipine belongs to the dihydropyridine (DHP) class of calcium channel blockers (CCBs), the most widely used class of CCBs. It is structurally related to felodipine, nifedipine, and nimodipine and is the most potent calcium-channel blocking agent of the DHP class. Isradipine binds to calcium channels with high affinity and specificity and inhibits calcium flux into cardiac and arterial smooth muscle cells. It exhibits greater selectivity towards arterial smooth muscle cells owing to alternative splicing of the alpha-1 subunit of the channel and increased prevalence of inactive channels in smooth muscle cells. Isradipine may be used to treat mild to moderate essential hypertension. |
| CAS Number: | 75695-93-1 |
| Molecular Weight: | 371.3871 |
| DrugBank Indication: | For the management of mild to moderate essential hypertension. It may be used alone or concurrently with thiazide-type diuretics. |
| DrugBank Pharmacology: | Isradipine decreases arterial smooth muscle contractility and subsequent vasoconstriction by inhibiting the influx of calcium ions through L-type calcium channels. Calcium ions entering the cell through these channels bind to calmodulin. Calcium-bound calmodulin then binds to and activates myosin light chain kinase (MLCK). Activated MLCK catalyzes the phosphorylation of the regulatory light chain subunit of myosin, a key step in muscle contraction. Signal amplification is achieved by calcium-induced calcium release from the sarcoplasmic reticulum through ryanodine receptors. Inhibition of the initial influx of calcium decreases the contractile activity of arterial smooth muscle cells and results in vasodilation. The vasodilatory effects of isradipine result in an overall decrease in blood pressure. |
| DrugBank MoA: | Isradipine belongs to the dihydropyridine (DHP) class of calcium channel blockers (CCBs), the most widely used class of CCBs. There are at least five different types of calcium channels in <i>Homo sapiens</i>: L-, N-, P/Q-, R- and T-type. CCBs target L-type calcium channels, the major channel in muscle cells that mediates contraction. Similar to other DHP CCBs, isradipine binds directly to inactive calcium channels stabilizing their inactive conformation. Since arterial smooth muscle depolarizations are longer in duration than cardiac muscle depolarizations, inactive channels are more prevalent in smooth muscle cells. Alternative splicing of the alpha-1 subunit of the channel gives isradipine additional arterial selectivity. At therapeutic sub-toxic concentrations, isradipine has little effect on cardiac myocytes and conduction cells. |
| Targets: | Voltage-dependent L-type calcium channel subunit alpha-1C inhibitor; Voltage-dependent calcium channel subunit alpha-2/delta-1 inhibitor; Voltage-dependent L-type calcium channel subunit beta-2 inhibitor; Voltage-dependent T-type calcium channel subunit alpha-1H inhibitor; Voltage-dependent calcium channel subunit alpha-2/delta-2 inhibitor; Voltage-dependent L-type calcium channel subunit alpha-1D inhibitor; Voltage-dependent L-type calcium channel subunit alpha-1S inhibitor |
| Inclusion Criteria: | Indication associated |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs |
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| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
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| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I12 | 10763 | Hypertension | An artery disease characterized by chronic elevated blood pressure in the arteries. https://en.wikipedia.org/wiki/Hypertension, https://www.ncbi.nlm.nih.gov/pubmed/24352797 | disease of anatomical entity/ cardiovascular system disease/vascular disease/ artery disease | Details |