Benazepril

Summary

Benazepril (CHEMBL838) is an approved small-molecule EC 3.4.15.1 (peptidyl-dipeptidase A) inhibitor (ATC C09AA07) targeting ACE; indicated across 9 conditions including cardiovascular disorder and diabetes mellitus.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: C09AA07
• Targets: 1 (ACE)
• Indications: 9 conditions
• Clinical trials: 25
• Chemistry: 424.5 Da · C24H28N2O5

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL838
Name	Benazepril
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	5362124
ChEBI	CHEBI:3011
ATC	C09AA07
Molecular formula	C24H28N2O5
Molecular weight	424.5
InChIKey	XPCFTKFZXHTYIP-PMACEKPBSA-N

SMILES: CCOC(=O)[C@H](CCC1=CC=CC=C1)N[C@H]2CCC3=CC=CC=C3N(C2=O)CC(=O)O

IUPAC name: 2-[(3S)-3-[[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino]-2-oxo-4,5-dihydro-3H-1-benzazepin-1-yl]acetic acid

ChEBI definition: A benzazepine that is benazeprilat in which the carboxy group of the 2-amino-4-phenylbutanoic acid moiety has been converted to the corresponding ethyl ester. It is used (generally as its hydrochloride salt) as a prodrug for the angiotensin-converting enzyme inhibitor benazeprilat in the treatment of hypertension and heart failure.

Pharmacological roles (ChEBI): EC 3.4.15.1 (peptidyl-dipeptidase A) inhibitor, prodrug.

Also known as: Benazepril, Benazepril sandoz, Briem, C09AA07, CGS-14824A, Cibacen ws, Cibacene, Forteekor, Lotrel, SID50112921, benazepril, BENAZEPRIL

Parent form; salt/anhydrous children: CHEMBL1694

Patent coverage: 7,523 distinct patent families (28,085 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 27,870 (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
ACE	Angiotensin-converting enzyme	Inhibition	8.8	0.7%	P12821

Broader ChEMBL bioactivity targets: 7 (assay-derived). Sample: Tyrosyl-DNA phosphodiesterase 1, Angiotensin-converting enzyme, cGMP-inhibited 3’,5’-cyclic phosphodiesterase 3A, Angiotensin-converting enzyme, Angiotensin-converting enzyme, Type-2 angiotensin II receptor, Bile salt export pump.

Bioactivity

ChEMBL activities: 8 potent at pChembl ≥ 5 of 10 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
P47820	8.77	IC50	1.7	nM	CHEMBL_ACT_562915
ACE	8.77	IC50	1.7	nM	CHEMBL_ACT_650072
P12822	8.7	IC50	2	nM	CHEMBL_ACT_657075
P12822	7	IC50	100	nM	CHEMBL_ACT_15631693
P12822	6.67	IC50	212	nM	CHEMBL_ACT_13397915
AGTR2	5.4	AC50	4000	nM	CHEMBL_ACT_25116864
PDE3A	5.16	AC50	7000	nM	CHEMBL_ACT_25191145
AGTR2	5.12	AC50	7500	nM	CHEMBL_ACT_25116890

Target pathways

Aggregated over 1 target gene(s): ACE.

Top Reactome pathways

3 total, by targets touching each:

Pathway	Targets	Genes
Metabolism of Angiotensinogen to Angiotensins	1	ACE
Peptide hormone metabolism	1	ACE
Metabolism of proteins	1	ACE

Dominant GO biological processes

GO term	Targets
kidney development	1
blood vessel remodeling	1
angiotensin maturation	1
regulation of renal output by angiotensin	1
neutrophil mediated immunity	1
antigen processing and presentation of peptide antigen via MHC class I	1
regulation of systemic arterial blood pressure by renin-angiotensin	1
positive regulation of systemic arterial blood pressure	1
proteolysis	1
spermatogenesis	1
regulation of blood pressure	1
male gonad development	1
post-transcriptional regulation of gene expression	1
negative regulation of gene expression	1
substance P catabolic process	1

Indications & clinical

Indications

9 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
diabetes mellitus	3	MONDO:0005015	EFO:0000400
hypertensive disorder	3	MONDO:0005044	EFO:0000537
atherosclerosis	3	MONDO:0005311	EFO:0003914
coronary artery disorder	3	MONDO:0005010	EFO:0001645
type 2 diabetes mellitus	3	MONDO:0005148	MONDO:0005148
hereditary nephritis	2	MONDO:0005334	MONDO:0018965
systemic lupus erythematosus	2	MONDO:0007915	MONDO:0007915

1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 25.

Phase distribution

Phase	Trials
PHASE4	8
Not specified	5
PHASE3	4
PHASE1	4
PHASE2	3
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00136773	PHASE4	COMPLETED	Effects of Amlodipine/Benazepril on Albuminuria in Hypertensive Patients With Type 2 Diabetes Mellitus
NCT00136851	PHASE4	COMPLETED	Study Comparing the Efficacy of Amlodipine Besylate/Benazepril Versus Amlodipine in the Treatment of Severe Hypertension
NCT00139555	PHASE4	COMPLETED	Effects of Amlodipine/Benazepril in Reducing Left Ventricular Hypertrophy in Patients With High Risk Hypertension
NCT00185120	PHASE4	COMPLETED	Treatment of High Blood Pressure Using Olmesartan With Hydrochlorothiazide Compared to an ACE Inhibitor With a Calcium Channel Blocker
NCT00367978	PHASE4	COMPLETED	Effects of Amlodipine/Benazepril in the Hypertensive African-American Population With Type 2 Diabetes Mellitus
NCT01375322	PHASE4	COMPLETED	ADDM Study - Amtrel and Co-Diovan in Type 2 Diabetes Mellitus Hypertension Patients With Microalbuminuria
NCT01603940	PHASE4	COMPLETED	Comparison Between Losartan and Benazepril in Diabetic Hypertensive Patients Not Controlled by Amlodipine
NCT01917149	PHASE4	COMPLETED	Supramaximal Titrated Inhibition of RAAS in Dilated Cardiomyopathy
NCT00171366	PHASE3	COMPLETED	A Study Comparing the Response of Patients With Hypertension to Amlodipine or Amlodipine Plus Benazepril.
NCT00494715	PHASE3	COMPLETED	Preventing ESRD in Overt Nephropathy of Type 2 Diabetes
NCT00503152	PHASE3	COMPLETED	Preventing Microalbuminuria in Type 2 Diabetes
NCT01095939	PHASE3	COMPLETED	Post-preeclampsia Renal Project: Study of Nephroprotection in Women Having Suffered Preeclampsia
NCT04486118	PHASE2	ACTIVE_NOT_RECRUITING	Centrally Acting ACE Inhibition in SLE
NCT01234922	PHASE2	TERMINATED	Benazepril Hydrochloride, Lisinopril, Ramipril, or Losartan Potassium in Treating Hypertension in Patients With Solid Tumors
NCT03591471	PHASE1/PHASE2	UNKNOWN	Study on Children Henoch-Schönlein Purpura Nephritis With TCM Multistep Treatment
NCT04937907	PHASE2	COMPLETED	Study of Hydroxychloroquine in Patients With X-linked Alport Syndrome in China (CHXLAS)
NCT00649038	PHASE1	COMPLETED	Fed Study of Benazepril HCl and Hydrochlorothiazide Tablets 20 mg/25 mg to Lotensin HCT® Tablets 20 mg/25 mg
NCT00649597	PHASE1	COMPLETED	Fasting Study of Benazepril HCl and Hydrochlorothiazide Tablets 20 mg/25 mg to Lotensin HCT® Tablets 20 mg/25 mg
NCT01155895	PHASE1	COMPLETED	Bioequivalence Study of 10 mg Amlodipine Besylate/ 20 mg Benazepril Hydrochloride Capsules of Dr.Reddys Laboratories Limited Under Fasting Conditions
NCT01155908	PHASE1	COMPLETED	Bioequivalence Study of 10 mg Amlodipine Besylate/ 20 mg Benazepril Hydrochloride Capsules of Dr.Reddys Laboratories Limited Under Non-fasting (Fed) Conditions
NCT00270426	Not specified	TERMINATED	Benazepril for Advanced Chronic Renal Insufficiency
NCT00338091	Not specified	TERMINATED	Long-Term Renoprotection of Optimal Antiproteinuric Doses of Benazepril and Losartan in Chronic Renal Insufficiency
NCT00630708	Not specified	TERMINATED	Safety of Dual Blockage of Rennin-angiotensin System in Patients With Advanced Renal Insufficiency
NCT00721773	Not specified	COMPLETED	Renal Protective Effects of Renin Angiotensin System (RAS) Inhibitor in Peritoneal Dialysis Patients
NCT00907374	Not specified	COMPLETED	Low Dose Versus Aggressive Inhibition of the Renin-Angiotensin-Aldosterone (RAS) to Treat Microalbuminuria

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 8 clinical and 25 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

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.

32 molecules share ≥1 primary target. Top 32 by shared-target count:

Molecule	Source	Status	Shared targets
CAPTOPRIL	ChEMBL + PubChem	Phase 4 (approved)	ACE
LOSARTAN	ChEMBL + PubChem	Phase 4 (approved)	ACE
PERINDOPRIL	ChEMBL + PubChem	Phase 4 (approved)	ACE
SITAGLIPTIN	ChEMBL + PubChem	Phase 4 (approved)	ACE
ENALAPRIL	ChEMBL	Phase 4 (approved)	ACE
ENALAPRILAT	ChEMBL	Phase 4 (approved)	ACE
FOSINOPRIL	ChEMBL	Phase 4 (approved)	ACE
IMIDAPRIL	ChEMBL	Phase 4 (approved)	ACE
LISINOPRIL	ChEMBL	Phase 4 (approved)	ACE
MOEXIPRIL	ChEMBL	Phase 4 (approved)	ACE
QUINAPRIL	ChEMBL	Phase 4 (approved)	ACE
RAMIPRIL	ChEMBL	Phase 4 (approved)	ACE
TELMISARTAN	ChEMBL	Phase 4 (approved)	ACE
TRANDOLAPRIL	ChEMBL	Phase 4 (approved)	ACE
EDETIC ACID	ChEMBL	Phase 3	ACE
QUINAPRILAT	ChEMBL + PubChem	Phase 2 (approved)	ACE
BENAZEPRILAT	ChEMBL	Phase 2	ACE
CERONAPRIL	ChEMBL	Phase 2	ACE
FOSINOPRILAT	ChEMBL	Phase 2	ACE
IMIDAPRILAT	ChEMBL	Phase 2	ACE
LIBENZAPRIL	ChEMBL	Phase 2	ACE
MOEXIPRILAT	ChEMBL	Phase 2	ACE
OMAPATRILAT	ChEMBL	Phase 2	ACE
PROLINE	ChEMBL	Phase 2	ACE
RENTIAPRIL	ChEMBL	Phase 2	ACE
SAMPATRILAT	ChEMBL	Phase 2	ACE
SPIRAPRILAT	ChEMBL	Phase 2	ACE
TEPROTIDE	ChEMBL	Phase 2	ACE
ZOFENOPRIL	ChEMBL	Phase 2	ACE
Gallic Acid	PubChem	Approved	ACE
Hydrochlorothiazide	PubChem	Approved	ACE
Paclitaxel	PubChem	Approved	ACE