Lisinopril Anhydrous

Summary

Lisinopril Anhydrous (CHEMBL1237) is an approved small-molecule EC 3.4.15.1 (peptidyl-dipeptidase A) inhibitor targeting ACE; indicated across 28 conditions including cardiovascular disorder and diabetes mellitus.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• Targets: 1 (ACE)
• Indications: 28 conditions
• Clinical trials: 85
• Chemistry: 405.5 Da · C21H31N3O5

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1237
Name	Lisinopril Anhydrous
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	5362119
ChEBI	CHEBI:43755
Molecular formula	C21H31N3O5
Molecular weight	405.5
InChIKey	RLAWWYSOJDYHDC-BZSNNMDCSA-N

SMILES: C1C[C@H](N(C1)C(=O)[C@H](CCCCN)N[C@@H](CCC2=CC=CC=C2)C(=O)O)C(=O)O

IUPAC name: (2S)-1-[(2S)-6-amino-2-[[(1S)-1-carboxy-3-phenylpropyl]amino]hexanoyl]pyrrolidine-2-carboxylic acid

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

Also known as: Lisinopril anhydrous, Lisinopril, lisinopril, SID50085996, LISINOPRIL, LISINOPRIL ANHYDROUS

Parent form; salt/anhydrous children: CHEMBL419213, CHEMBL1729579

Patent coverage: 14,779 distinct patent families (56,016 SureChEMBL compound mentions), from 1 matched compound structure(s). 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	9.4	0.7%	P12821

Broader ChEMBL bioactivity targets: 2 (assay-derived). Sample: Angiotensin-converting enzyme, Angiotensin-converting enzyme.

Bioactivity

ChEMBL activities: 20 potent at pChembl ≥ 5 of 20 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
ACE	10	IC50	0.1	nM	CHEMBL_ACT_1006457
ACE	10	IC50	0.1	nM	CHEMBL_ACT_13501387
ACE	10	IC50	0.1	nM	CHEMBL_ACT_24867617
ACE	8.92	Ki	1.2	nM	CHEMBL_ACT_24394799
ACE	8.92	IC50	1.2	nM	CHEMBL_ACT_25090608
ACE	8.92	IC50	1.2	nM	CHEMBL_ACT_737308
ACE	8.92	IC50	1.2	nM	CHEMBL_ACT_83360
ACE	8.92	IC50	1.2	nM	CHEMBL_ACT_938515
ACE	8.33	IC50	4.7	nM	CHEMBL_ACT_658562
ACE	8.32	Ki	4.8	nM	CHEMBL_ACT_24394804
P12822	8.22	IC50	6.04	nM	CHEMBL_ACT_7757505
ACE	8.1	IC50	7.92	nM	CHEMBL_ACT_18326566
ACE	7.62	Kd	24	nM	CHEMBL_ACT_29297828
P12822	7.29	Ki	51	nM	CHEMBL_ACT_1760814
ACE	7.29	Ki	51	nM	CHEMBL_ACT_1760978
ACE	6.88	Ki	131.5	nM	CHEMBL_ACT_1760815
ACE	6.88	Ki	131.5	nM	CHEMBL_ACT_1760979
P12822	6.58	IC50	262	nM	CHEMBL_ACT_13397917
P12822	6.55	IC50	281	nM	CHEMBL_ACT_15111544
P12822	6.5	IC50	318	nM	CHEMBL_ACT_15631691

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

28 indications (0 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	3	MONDO:0004995	EFO:0000319
diabetes mellitus	3	MONDO:0005015	EFO:0000400
diabetic kidney disease	3	MONDO:0005016	EFO:0000401
hypertensive disorder	3	MONDO:0005044	EFO:0000537
heart failure	3	MONDO:0005252	EFO:0003144
myocardial infarction	3	MONDO:0005068	EFO:0000612
atherosclerosis	3	MONDO:0005311	EFO:0003914
polycystic kidney disease	3	MONDO:0020642	EFO:0008620
myocardial ischemia	3	MONDO:0024644	EFO:1001375
congestive heart failure	3	MONDO:0005009	EFO:0000373
coronary artery disorder	3	MONDO:0005010	EFO:0001645
primary hyperoxaluria	3	MONDO:0002474	MONDO:0002474
type 2 diabetes mellitus	3	MONDO:0005148	MONDO:0005148
spermatogenic failure	2	MONDO:0004983	EFO:0000279
focal segmental glomerulosclerosis	2	MONDO:0100313	EFO:0004236
glomerulonephritis	2	MONDO:0002462	MONDO:0002462
breast neoplasm	2	MONDO:0021100	MONDO:0007254
metabolic dysfunction-associated steatohepatitis	2	MONDO:0007027	EFO:1001249
hepatocellular carcinoma	2	MONDO:0007256	EFO:0000182
essential hypertension	2	MONDO:0001134	MONDO:0001134
cardiomyopathy	2	MONDO:0004994	EFO:0000318
systemic lupus erythematosus	2	MONDO:0007915	MONDO:0007915
stroke disorder	1	MONDO:0005098	EFO:0000712
vascular disorder	1	MONDO:0005385	EFO:0004264
gastroparesis	1	MONDO:0006769	EFO:1000948

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

Clinical trials

Total trials: 85.

Phase distribution

Phase	Trials
PHASE4	18
Not specified	18
PHASE1	17
PHASE2	15
PHASE3	14
PHASE2/PHASE3	1
PHASE1/PHASE2	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07547878	PHASE4	NOT_YET_RECRUITING	Rapid and Simultaneous Initiation of Four Guideline-Directed CKD Therapies (RAPID-CKD)
NCT07594535	PHASE4	NOT_YET_RECRUITING	The Effect Of Lisinopril On Polycythemia
NCT00171574	PHASE4	COMPLETED	Antiproteinuric Effect of Valsartan and Lisinopril
NCT00171600	PHASE4	TERMINATED	Antialbuminuric Effects of Valsartan and Lisinopril
NCT00241124	PHASE4	COMPLETED	Comparison Of Morning And Evening Dosing Of Valsartan And Lisinopril In Patients With Diabetes
NCT00311870	PHASE4	COMPLETED	Renoprotective Effect of Nisoldipine and Lisinopril in Type 1 Diabetic Nephropathy
NCT00391846	PHASE4	COMPLETED	Evaluation of Heart Failure Treatment Guided by N-terminal Pro B-type Natriuretic Peptide (NTproBNP) vs Clinical Symptoms and Signs Alone
NCT00430040	PHASE4	TERMINATED	Vascular Benefits of Adding CarvedilolCR to Type2 Diabetic Patients on ACEI.
NCT00661895	PHASE4	COMPLETED	Black Education and Treatment of Hypertension (BEAT HTN)
NCT01218100	PHASE4	COMPLETED	Efficacy and Safety Study to Evaluate Combination Therapy With Nebivolol and Lisinopril vs. Placebo and Monotherapy in Patients With Stage 2 Diastolic Hypertension
NCT01535235	PHASE4	COMPLETED	ACE Inhibitors to Decrease Lymphoid Fibrosis in Antiretroviral-Treated, HIV-infected Patients: A Pilot Study
NCT01837069	PHASE4	TERMINATED	Risk Factor Control Before Orthopedic Surgery
NCT02184858	PHASE4	COMPLETED	Dose Titration of Lisinopril in Children Aged 1 to 18 Years With Primary or Secondary Hypertension
NCT02441842	PHASE4	COMPLETED	Evaluation of Periop Biochemical Stress Factors in Craniotomy Neurosurgical Procedure With Respect to Preop Hypertension
NCT02847338	PHASE4	COMPLETED	Comparison of Optimal Hypertension Regimens
NCT03195023	PHASE4	UNKNOWN	Effect of RAS Blockers on CKD Progression in Elderly Patients With Non Proteinuric Nephropathies (PROERCAN01)
NCT03392740	PHASE4	WITHDRAWN	Prophylactic Lisinopril to Prevent Anthracycline Cardiomyopathy.
NCT03461003	PHASE4	COMPLETED	N-of-1 Trials In Children With Hypertension
NCT00000542	PHASE3	COMPLETED	Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)
NCT00004266	PHASE3	COMPLETED	Drugs for High Blood Pressure and High Cholesterol in American Indians With Type 2 Diabetes
NCT00108082	PHASE3	COMPLETED	The CLEVER Study - Coreg And Left Ventricular Mass Regression
NCT00123903	PHASE3	TERMINATED	COREG MR Versus TOPROL-XL On Reduction Of Microalbuminuria In Patients With Hypertension And Microalbuminuria
NCT00171067	PHASE3	COMPLETED	VALERIA: Valsartan in Combination With Lisinopril in Hypertensive Patients With Microalbuminuria
NCT00283686	PHASE3	COMPLETED	HALT Progression of Polycystic Kidney Disease Study A
NCT00347360	PHASE3	COMPLETED	The COREG And Lisinopril Combination Therapy In Hypertensive Subjects (COSMOS) Trial
NCT00459056	PHASE3	COMPLETED	The Vascular Effects of Carvedilol Controlled Release (CR) in Abdominally Obese Hypertensive Patients
NCT00555217	PHASE3	TERMINATED	VA NEPHRON-D: Diabetes iN Nephropathy Study
NCT00582114	PHASE3	TERMINATED	Hypertension in Hemodialysis Patients (Aim 3)
NCT00624065	PHASE3	COMPLETED	Research Study To Test Carvedilol CR + Lisinopril Versus Lisinopril + Placebo In Patients With High Blood Pressure
NCT01126697	PHASE2/PHASE3	COMPLETED	Clinical Trial of Coenzyme Q10 and Lisinopril in Muscular Dystrophies
NCT01437371	PHASE3	COMPLETED	Is There a Benefit to Optimize Heart Failure (HF) Treatment in Aged Over 80 Year’s Old Patients?
NCT01885559	PHASE3	COMPLETED	HALT Progression of Polycystic Kidney Disease Study B
NCT05056727	PHASE3	TERMINATED	A Study to Evaluate the Effect of Sodium Zirconium Cyclosilicate on Chronic Kidney Disease (CKD) Progression in Participants With CKD and Hyperkalaemia or at Risk of Hyperkalaemia
NCT04486118	PHASE2	ACTIVE_NOT_RECRUITING	Centrally Acting ACE Inhibition in SLE
NCT04550481	PHASE2	ACTIVE_NOT_RECRUITING	Role of Lisinopril in Preventing the Progression of Non-Alcoholic Fatty Liver Disease, RELIEF-NAFLD Study
NCT00553969	PHASE1/PHASE2	COMPLETED	Efficacy of Coreg CR and Lisinopril on Markers for Cardiovascular Functional and Structural Disease
NCT00605072	PHASE2	COMPLETED	The Antihypertensives and Vascular, Endothelial and Cognitive Function Trial
NCT00874432	PHASE2	COMPLETED	Effect of ACE-inhibitors on Aortic Stiffness in Elderly Patients With Chronic Kidney Disease
NCT01009918	PHASE2	COMPLETED	Lisinopril or Coreg CR® in Reducing Side Effects in Women With Breast Cancer Receiving Trastuzumab
NCT01234922	PHASE2	TERMINATED	Benazepril Hydrochloride, Lisinopril, Ramipril, or Losartan Potassium in Treating Hypertension in Patients With Solid Tumors

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 10 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
BENAZEPRIL	ChEMBL	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
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