Nisoldipine

Summary

Nisoldipine (CHEMBL1726) is an approved small molecule (ATC C08CA07) targeting CACNA1C and CACNA1D; indicated across 2 conditions including cardiovascular disorder and hypertensive disorder.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: C08CA07
• Targets: 2 (CACNA1C, CACNA1D)
• Indications: 2 conditions
• Clinical trials: 2
• Chemistry: 388.4 Da · C20H24N2O6

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1726
Name	Nisoldipine
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	4499
ChEBI	CHEBI:76917
ATC	C08CA07
Molecular formula	C20H24N2O6
Molecular weight	388.4
InChIKey	VKQFCGNPDRICFG-UHFFFAOYSA-N

SMILES: CC1=C(C(C(=C(N1)C)C(=O)OCC(C)C)C2=CC=CC=C2[N+](=O)[O-])C(=O)OC

IUPAC name: 3-O-methyl 5-O-(2-methylpropyl) 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate

ChEBI definition: A dihydropyridine that is 1,4-dihydropyridine which is substituted by methyl groups at positions 2 and 6, a methoxycarbonyl group at position 3, an o-nitrophenyl group at position 4, and an isobutoxycarbonyl group at position 5. The racemate, a calcium channel blocker, is used in the treatment of hypertension and angina pectoris.

Also known as: BAY K 5552, BAY-K-5552, Baymycard, Geomatrix 16e, Nisocor, Nisoldipin, Nisoldipine, Nisoldipine (stn), Nisoldipino, NSC-759106, Sular, Syscor mr 10

Patent coverage: 4,840 distinct patent families (18,921 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 18,918 (100%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
CACNA1C	Cav1.2	Antagonist	7.1	0.1%	Q13936
CACNA1D	Cav1.3		7	0.3%	Q01668

Broader ChEMBL bioactivity targets: 27 (assay-derived). Sample: Nuclear receptor ROR-gamma, Prelamin-A/C, 4’-phosphopantetheinyl transferase ffp, ATP-binding cassette sub-family C member 4, 5-hydroxytryptamine receptor 2B, Voltage-dependent L-type calcium channel subunit alpha-1C, Sodium channel protein type 5 subunit alpha, Glucocorticoid receptor, Progesterone receptor, Sodium channel alpha subunits; brain (Types I, II, III), Nuclear receptor subfamily 1 group I member 2, Cannabinoid receptor 1, Adenosine receptor A1, Alpha-1A adrenergic receptor, Mu-type opioid receptor, D(3) dopamine receptor, Voltage-dependent L-type calcium channel subunit alpha-1C, Voltage-gated inwardly rectifying potassium channel KCNH2, cGMP-inhibited 3’,5’-cyclic phosphodiesterase 3A, Adenosine receptor A2a.

Bioactivity

ChEMBL activities: 22 potent at pChembl ≥ 5 of 39 total. Top 100 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
CACNA1C	8.52	IC50	3	nM	CHEMBL_ACT_15373265
O35505	7.1	IC50	80	nM	CHEMBL_ACT_15373266
ADORA3	6.21	AC50	614	nM	CHEMBL_ACT_25134276
O35505	6.14	IC50	730	nM	CHEMBL_ACT_15373267
CYP1A2	6	IC50	1000	nM	CHEMBL_ACT_7731353
ADORA2A	5.64	Ki	2278	nM	CHEMBL_ACT_7731288
NR1I2	5.48	AC50	3300	nM	CHEMBL_ACT_25188220
ADORA2A	5.39	IC50	4058	nM	CHEMBL_ACT_7731287
ADORA3	5.39	Ki	4024	nM	CHEMBL_ACT_7731290
P22002	5.33	AC50	4624	nM	CHEMBL_ACT_25119643
PGR	5.31	AC50	4900	nM	CHEMBL_ACT_25222185
ADORA2A	5.26	AC50	5500	nM	CHEMBL_ACT_25152545
PDE3A	5.21	AC50	6200	nM	CHEMBL_ACT_25190759
ADORA3	5.15	IC50	7120	nM	CHEMBL_ACT_7731289
NR1I2	5.1	EC50	7900	nM	CHEMBL_ACT_15465497
ABCB11	5.1	AC50	8000	nM	CHEMBL_ACT_25127042
LMNA	5.1	Potency	7943	nM	CHEMBL_ACT_3647275
SCN5A	5.07	AC50	8600	nM	CHEMBL_ACT_25158932
NR3C1	5.06	AC50	8800	nM	CHEMBL_ACT_25175906
OPRM1	5.03	AC50	9400	nM	CHEMBL_ACT_25157494
NR1I2	5	EC50	10000	nM	CHEMBL_ACT_15463757
DRD3	5	AC50	10000	nM	CHEMBL_ACT_25193593

Target pathways

Aggregated over 2 target gene(s): CACNA1C, CACNA1D.

Top Reactome pathways

16 total, by targets touching each:

Pathway	Targets	Genes
Developmental Biology	2	CACNA1C, CACNA1D
Metabolism	2	CACNA1C, CACNA1D
Integration of energy metabolism	2	CACNA1C, CACNA1D
NCAM signaling for neurite out-growth	2	CACNA1C, CACNA1D
Adrenaline,noradrenaline inhibits insulin secretion	2	CACNA1C, CACNA1D
NCAM1 interactions	2	CACNA1C, CACNA1D
Regulation of insulin secretion	2	CACNA1C, CACNA1D
Axon guidance	2	CACNA1C, CACNA1D
Nervous system development	2	CACNA1C, CACNA1D
Muscle contraction	1	CACNA1C
Cardiac conduction	1	CACNA1C
Phase 0 - rapid depolarisation	1	CACNA1C
Phase 2 - plateau phase	1	CACNA1C
Sensory processing of sound	1	CACNA1D
Sensory processing of sound by inner hair cells of the cochlea	1	CACNA1D
Sensory Perception	1	CACNA1D

Dominant GO biological processes

GO term	Targets
positive regulation of adenylate cyclase activity	2
calcium ion transmembrane transport	2
cardiac muscle cell action potential involved in contraction	2
membrane depolarization during cardiac muscle cell action potential	2
regulation of heart rate by cardiac conduction	2
calcium ion import across plasma membrane	2
monoatomic ion transport	2
calcium ion transport	2
muscle contraction	2
cell communication	2
signaling	2
monoatomic ion transmembrane transport	2
transmembrane transport	2
immune system development	1
positive regulation of cytosolic calcium ion concentration	1

Indications & clinical

Indications

2 approved indications. FDA phase 4, plus an anticancer drug’s labelled cancer uses (which ChEMBL often logs at phase 3).

Indication	Phase	MONDO	EFO
cardiovascular disorder	4	MONDO:0004995	EFO:0000319
hypertensive disorder	4	MONDO:0005044	EFO:0000537

Clinical trials

Total trials: 2.

Phase distribution

Phase	Trials
PHASE4	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00311870	PHASE4	COMPLETED	Renoprotective Effect of Nisoldipine and Lisinopril in Type 1 Diabetic Nephropathy
NCT00979537	PHASE1	COMPLETED	Single-Dose Fed Bioequivalence Study of Nisoldipine Extended-Release Tablets (40 mg; Mylan) and Sular® Extended-Release Tablets (40 mg; First Horizon) in Healthy Volunteers

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

113 molecules share ≥1 primary target. Top 100 by shared-target count:

Molecule	Source	Status	Shared targets
AMIODARONE	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D
AMITRIPTYLINE	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D
AMLODIPINE	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D
CHLORPROMAZINE	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D
CILOSTAZOL	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D
CLOZAPINE	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D
DIAZEPAM	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D
DILTIAZEM	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D
DOFETILIDE	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D
DONEPEZIL	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D
DROPERIDOL	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D
DULOXETINE	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D
FLECAINIDE	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D
HALOPERIDOL	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D
IBUTILIDE	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D
IMIPRAMINE	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D
ISRADIPINE	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D
LAMIVUDINE	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D
LORATADINE	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D
METHADONE	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D
MEXILETINE	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D
MITOXANTRONE	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D
NIFEDIPINE	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D
NILOTINIB	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D
NIMODIPINE	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D
PAROXETINE	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D
PHENYTOIN	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D
PIMOZIDE	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D
QUINIDINE	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D
RISPERIDONE	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D
SAQUINAVIR	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D
SOLIFENACIN	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D
SUNITINIB	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D
THIORIDAZINE	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D
VERAPAMIL	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	CACNA1C, CACNA1D
BEPRIDIL	ChEMBL	Phase 4 (approved)	CACNA1C, CACNA1D
CISAPRIDE	ChEMBL	Phase 4 (approved)	CACNA1C, CACNA1D
DASATINIB	ChEMBL	Phase 4 (approved)	CACNA1C, CACNA1D
HALOFANTRINE	ChEMBL	Phase 4 (approved)	CACNA1C, CACNA1D
MIBEFRADIL	ChEMBL	Phase 4 (approved)	CACNA1C, CACNA1D
SERTINDOLE	ChEMBL	Phase 4 (approved)	CACNA1C, CACNA1D
SPARFLOXACIN	ChEMBL	Phase 4 (approved)	CACNA1C, CACNA1D
TACRINE	ChEMBL	Phase 4 (approved)	CACNA1C, CACNA1D
TERFENADINE	ChEMBL	Phase 4 (approved)	CACNA1C, CACNA1D
TERODILINE	ChEMBL	Phase 4 (approved)	CACNA1C, CACNA1D
AJMALINE	ChEMBL	Phase 3	CACNA1C, CACNA1D
NITRENDIPINE	ChEMBL	Phase 3	CACNA1C, CACNA1D
CIFENLINE	ChEMBL	Phase 2	CACNA1C, CACNA1D
GALLOPAMIL	ChEMBL	Phase 2	CACNA1C, CACNA1D
Belzutifan	PubChem	Approved	CACNA1C, CACNA1D
Moxifloxacin	PubChem	Approved	CACNA1C, CACNA1D
Paliperidone	PubChem	Approved	CACNA1C, CACNA1D
SILDENAFIL	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C
VARDENAFIL	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C
ALVIMOPAN	ChEMBL	Phase 4 (approved)	CACNA1C
CLEMASTINE	ChEMBL	Phase 4 (approved)	CACNA1C
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	CACNA1C
DIBUCAINE	ChEMBL	Phase 4 (approved)	CACNA1C
DORIPENEM	ChEMBL	Phase 4 (approved)	CACNA1C
ESTRADIOL	ChEMBL	Phase 4 (approved)	CACNA1C
FLUOXETINE	ChEMBL	Phase 4 (approved)	CACNA1C
FLUSPIRILENE	ChEMBL	Phase 4 (approved)	CACNA1C
KETAMINE	ChEMBL	Phase 4 (approved)	CACNA1C
LACOSAMIDE	ChEMBL	Phase 4 (approved)	CACNA1C
NEBIVOLOL	ChEMBL	Phase 4 (approved)	CACNA1C
NICARDIPINE	ChEMBL	Phase 4 (approved)	CACNA1C
OLICERIDINE	ChEMBL	Phase 4 (approved)	CACNA1C
PINAVERIUM	ChEMBL	Phase 4 (approved)	CACNA1C
PITOLISANT	ChEMBL	Phase 4 (approved)	CACNA1C
PRENYLAMINE	ChEMBL	Phase 4 (approved)	CACNA1C
PROPAFENONE	ChEMBL	Phase 4 (approved)	CACNA1C
PROPIVERINE	ChEMBL	Phase 4 (approved)	CACNA1C
PROPRANOLOL	ChEMBL	Phase 4 (approved)	CACNA1C
REMIFENTANIL	ChEMBL	Phase 4 (approved)	CACNA1C
SERTRALINE	ChEMBL	Phase 4 (approved)	CACNA1C
TESTOSTERONE	ChEMBL	Phase 4 (approved)	CACNA1C
TOLTERODINE	ChEMBL	Phase 4 (approved)	CACNA1C
XANOMELINE	ChEMBL	Phase 4 (approved)	CACNA1C
BENIDIPINE	ChEMBL	Phase 3	CACNA1C
CETYLPYRIDINIUM	ChEMBL	Phase 3	CACNA1C
CILNIDIPINE	ChEMBL	Phase 3	CACNA1C
APINOCALTAMIDE	ChEMBL	Phase 2	CACNA1C
BARNIDIPINE	ChEMBL	Phase 2	CACNA1C
CARVACROL	ChEMBL	Phase 2	CACNA1C
SELICICLIB	ChEMBL	Phase 2	CACNA1C
Z160	ChEMBL	Phase 2	CACNA1C
Apremilast	PubChem	Approved	CACNA1C
Baloxavir	PubChem	Approved	CACNA1C
Binimetinib	PubChem	Approved	CACNA1C
Ceftriaxone	PubChem	Approved	CACNA1D
Crizotinib	PubChem	Approved	CACNA1C
Desvenlafaxine	PubChem	Approved	CACNA1C
Disopyramide	PubChem	Approved	CACNA1D
Enzalutamide	PubChem	Approved	CACNA1C
Erythromycin	PubChem	Approved	CACNA1C
Inavolisib	PubChem	Approved	CACNA1C
Linezolid	PubChem	Approved	CACNA1D
Melatonin	PubChem	Approved	CACNA1D
Metronidazole	PubChem	Approved	CACNA1D