Nitrendipine

Summary

Nitrendipine (CHEMBL475534) is a phase-3 clinical-stage small-molecule calcium channel blocker (ATC C08CA08) targeting KCNN4, CACNA1S, and CACNA1C; indicated across 2 conditions including cardiovascular disorder and hypertensive disorder.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• ATC class: C08CA08
• Targets: 5 (KCNN4, CACNA1S, CACNA1C…)
• Indications: 2 conditions
• Clinical trials: 5
• Chemistry: C18H20N2O6

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL475534
Name	Nitrendipine
Type	Small molecule
Max phase	3
ChEBI	CHEBI:7582
ATC	C08CA08
Molecular formula	C18H20N2O6
InChIKey	PVHUJELLJLJGLN-UHFFFAOYSA-N

SMILES: CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1c1cccc([N+](=O)[O-])c1

ChEBI definition: A dihydropyridine that is 1,4-dihydropyridine substituted by methyl groups at positions 2 and 6, a 3-nitrophenyl group at position 4, a ethoxycarbonyl group at position 3 and a methoxycarbonyl group at position 5. It is a calcium-channel blocker used in the treatment of hypertension.

Pharmacological roles (ChEBI): calcium channel blocker, antihypertensive agent, vasodilator agent, geroprotector.

Also known as: (+/-)-BAY-E-5009, BAY E 5009, BAY-E-5009, Bayotensin, Baypress, Deiten, Nidrel, Nitrendipine, Nitrendipino, Nitrepin, NSC-758466, SID26751794

Patent coverage: 4,738 distinct patent families (16,468 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 16,353 (99%) 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
KCNN4	KCa3.1	Inhibition	6.1	0.2%	O15554
CACNA1S	Cav1.1	Antagonist	6	0.2%	Q13698
CACNA1C	Cav1.2	Antagonist	9.4	0.1%	Q13936
CACNA1D	Cav1.3	Inhibition	8.4	0.3%	Q01668
CACNA1F	Cav1.4	Antagonist	6	0%	O60840

Broader ChEMBL bioactivity targets: 33 (assay-derived). Sample: Transient receptor potential cation channel subfamily A member 1, Microtubule-associated protein tau, Prelamin-A/C, RecQ-like DNA helicase BLM, Inositol monophosphatase 1, Ferritin light chain, Geminin, Peripheral myelin protein 22, Voltage-dependent L-type calcium channel subunit alpha-1C, Sodium channel protein type 5 subunit alpha.

Bioactivity

ChEMBL activities: 26 potent at pChembl ≥ 5 of 47 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
CACNA1F	9.82	IC50	0.15	nM	CHEMBL_ACT_703862
CACNA1C	9.6	Ki	0.25	nM	CHEMBL_ACT_109960
CACNA1C	9.59	Kd	0.26	nM	CHEMBL_ACT_813022
CACNA1F	9.46	IC50	0.35	nM	CHEMBL_ACT_15257935
P22002	9.4	AC50	0.4	nM	CHEMBL_ACT_25119376
CACNA1F	9	IC50	1	nM	CHEMBL_ACT_1030535
P22002	8.89	IC50	1.3	nM	CHEMBL_ACT_5165989
CACNA1F	7.52	IC50	30	nM	CHEMBL_ACT_15373343
CYP2C9	6.52	IC50	300	nM	CHEMBL_ACT_7739938
CACNA1C	6.38	AC50	420	nM	CHEMBL_ACT_25159064
P97697	6.3	Potency	501.2	nM	CHEMBL_ACT_4406338
PDE1C	5.73	IC50	1850	nM	CHEMBL_ACT_24929397
CYP2C19	5.52	IC50	3000	nM	CHEMBL_ACT_7739936
Q8BLA8	5.42	EC50	3800	nM	CHEMBL_ACT_3301114
LMNA	5.4	Potency	3981	nM	CHEMBL_ACT_3637353
SCN5A	5.3	AC50	5000	nM	CHEMBL_ACT_25158852
NR1I2	5.27	AC50	5422	nM	CHEMBL_ACT_25187987
NR1I2	5.14	AC50	7225	nM	CHEMBL_ACT_25224202
ADORA3	5.08	Ki	8300	nM	CHEMBL_ACT_832742
P25099	5.05	Ki	8960	nM	CHEMBL_ACT_832740
KCNH2	5	IC50	10000	nM	CHEMBL_ACT_1054250
KCNH2	5	IC50	10000	nM	CHEMBL_ACT_1523709
KCNH2	5	IC50	10000	nM	CHEMBL_ACT_15257965
KCNH2	5	IC50	10000	nM	CHEMBL_ACT_2358290
GMNN	5	Potency	10000	nM	CHEMBL_ACT_5065035
KCNH2	5	IC50	10000	nM	CHEMBL_ACT_5218925

Target pathways

Aggregated over 5 target gene(s): KCNN4, CACNA1S, CACNA1C, CACNA1D, CACNA1F.

Top Reactome pathways

19 total, by targets touching each:

Pathway	Targets	Genes
Developmental Biology	3	CACNA1C, CACNA1D, CACNA1S
NCAM signaling for neurite out-growth	3	CACNA1C, CACNA1D, CACNA1S
NCAM1 interactions	3	CACNA1C, CACNA1D, CACNA1S
Axon guidance	3	CACNA1C, CACNA1D, CACNA1S
Nervous system development	3	CACNA1C, CACNA1D, CACNA1S
Metabolism	2	CACNA1C, CACNA1D
Integration of energy metabolism	2	CACNA1C, CACNA1D
Adrenaline,noradrenaline inhibits insulin secretion	2	CACNA1C, CACNA1D
Regulation of insulin secretion	2	CACNA1C, CACNA1D
Neuronal System	1	KCNN4
Ca2+ activated K+ channels	1	KCNN4
Potassium Channels	1	KCNN4
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
calcium ion transport	5
monoatomic ion transport	5
monoatomic ion transmembrane transport	5
calcium ion transmembrane transport	4
calcium ion import across plasma membrane	4
transmembrane transport	4
muscle contraction	3
positive regulation of muscle contraction	2
system process	2
positive regulation of adenylate cyclase activity	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
cell communication	2
signaling	2

Indications & clinical

Indications

2 indications (1 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
cardiovascular disorder	4	MONDO:0004995	EFO:0000319
hypertensive disorder	3	MONDO:0005044	EFO:0000537

Clinical trials

Total trials: 5.

Phase distribution

Phase	Trials
PHASE4	3
PHASE3	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00892892	PHASE4	WITHDRAWN	Sympathetic Nerve Activity in Renal Failure
NCT02217852	PHASE4	UNKNOWN	Treatment of Hypertension in Tibetan Adult Population
NCT04931108	PHASE4	UNKNOWN	The Effect of Nitrendipine/Atenolol Combination on Blood Pressure Variability.
NCT00751829	PHASE3	COMPLETED	Isolated Systolic Hypertension in the Elderly and Very Elderly
NCT04371874	Not specified	COMPLETED	The Standardized Management of Hypertension in Rural Shaanxi

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

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.

116 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
AMIODARONE	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D, CACNA1F, CACNA1S
AMITRIPTYLINE	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D, CACNA1F, CACNA1S
CHLORPROMAZINE	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D, CACNA1F, CACNA1S
CILOSTAZOL	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D, CACNA1F, CACNA1S
CLOZAPINE	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D, CACNA1F, CACNA1S
DIAZEPAM	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D, CACNA1F, CACNA1S
DILTIAZEM	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D, CACNA1F, CACNA1S
DOFETILIDE	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D, CACNA1F, CACNA1S
DONEPEZIL	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D, CACNA1F, CACNA1S
DROPERIDOL	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D, CACNA1F, CACNA1S
DULOXETINE	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D, CACNA1F, CACNA1S
FLECAINIDE	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D, CACNA1F, CACNA1S
HALOPERIDOL	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D, CACNA1F, CACNA1S
IBUTILIDE	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D, CACNA1F, CACNA1S
IMIPRAMINE	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D, CACNA1F, CACNA1S
LAMIVUDINE	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D, CACNA1F, CACNA1S
LORATADINE	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D, CACNA1F, CACNA1S
METHADONE	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D, CACNA1F, CACNA1S
MEXILETINE	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D, CACNA1F, CACNA1S
MITOXANTRONE	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D, CACNA1F, CACNA1S
NIFEDIPINE	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D, CACNA1F, CACNA1S
NILOTINIB	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D, CACNA1F, CACNA1S
NIMODIPINE	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D, CACNA1F, CACNA1S
Nisoldipine	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D, CACNA1F, CACNA1S
PAROXETINE	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D, CACNA1F, CACNA1S
PHENYTOIN	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D, CACNA1F, CACNA1S
PIMOZIDE	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D, CACNA1F, CACNA1S
QUINIDINE	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D, CACNA1F, CACNA1S
RISPERIDONE	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D, CACNA1F, CACNA1S
SAQUINAVIR	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D, CACNA1F, CACNA1S
SOLIFENACIN	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D, CACNA1F, CACNA1S
SUNITINIB	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D, CACNA1F, CACNA1S
THIORIDAZINE	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D, CACNA1F, CACNA1S
VERAPAMIL	ChEMBL + PubChem	Phase 4 (approved)	CACNA1C, CACNA1D, CACNA1F, CACNA1S
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	CACNA1C, CACNA1D, CACNA1F, CACNA1S
BEPRIDIL	ChEMBL	Phase 4 (approved)	CACNA1C, CACNA1D, CACNA1F, CACNA1S
CISAPRIDE	ChEMBL	Phase 4 (approved)	CACNA1C, CACNA1D, CACNA1F, CACNA1S
DASATINIB	ChEMBL	Phase 4 (approved)	CACNA1C, CACNA1D, CACNA1F, CACNA1S
HALOFANTRINE	ChEMBL	Phase 4 (approved)	CACNA1C, CACNA1D, CACNA1F, CACNA1S
MIBEFRADIL	ChEMBL	Phase 4 (approved)	CACNA1C, CACNA1D, CACNA1F, CACNA1S
SERTINDOLE	ChEMBL	Phase 4 (approved)	CACNA1C, CACNA1D, CACNA1F, CACNA1S
SPARFLOXACIN	ChEMBL	Phase 4 (approved)	CACNA1C, CACNA1D, CACNA1F, CACNA1S
TACRINE	ChEMBL	Phase 4 (approved)	CACNA1C, CACNA1D, CACNA1F, CACNA1S
TERFENADINE	ChEMBL	Phase 4 (approved)	CACNA1C, CACNA1D, CACNA1F, CACNA1S
TERODILINE	ChEMBL	Phase 4 (approved)	CACNA1C, CACNA1D, CACNA1F, CACNA1S
AJMALINE	ChEMBL	Phase 3	CACNA1C, CACNA1D, CACNA1F, CACNA1S
CIFENLINE	ChEMBL	Phase 2	CACNA1C, CACNA1D, CACNA1F, CACNA1S
GALLOPAMIL	ChEMBL	Phase 2	CACNA1C, CACNA1D, CACNA1F, CACNA1S
Belzutifan	PubChem	Approved	CACNA1C, CACNA1D, CACNA1F, CACNA1S
Moxifloxacin	PubChem	Approved	CACNA1C, CACNA1D, CACNA1F, CACNA1S
Paliperidone	PubChem	Approved	CACNA1C, CACNA1D, CACNA1F, CACNA1S
Ceftriaxone	PubChem	Approved	CACNA1D, CACNA1F, CACNA1S
Disopyramide	PubChem	Approved	CACNA1D, CACNA1F, CACNA1S
Linezolid	PubChem	Approved	CACNA1D, CACNA1F, CACNA1S
Melatonin	PubChem	Approved	CACNA1D, CACNA1F, CACNA1S
Metronidazole	PubChem	Approved	CACNA1D, CACNA1F, CACNA1S
Pemigatinib	PubChem	Approved	CACNA1D, CACNA1F, CACNA1S
Pentobarbital	PubChem	Approved	CACNA1D, CACNA1F, CACNA1S
Procainamide	PubChem	Approved	CACNA1D, CACNA1F, CACNA1S
Raltegravir	PubChem	Approved	CACNA1D, CACNA1F, CACNA1S