Ezetimibe

Summary

Ezetimibe (CHEMBL1138) is an approved small-molecule anticholesteremic drug (ATC C10AX09) targeting NPC1L1; indicated across 21 conditions including cardiovascular disorder and familial hypercholesterolemia.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: C10AX09
• Targets: 1 (NPC1L1)
• Indications: 21 conditions
• Clinical trials: 263
• Chemistry: 409.4 Da · C24H21F2NO3

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1138
Name	Ezetimibe
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	150311
ChEBI	CHEBI:49040
ATC	C10AX09
Molecular formula	C24H21F2NO3
Molecular weight	409.4
InChIKey	OLNTVTPDXPETLC-XPWALMASSA-N

SMILES: C1=CC(=CC=C1[C@@H]2[C@H](C(=O)N2C3=CC=C(C=C3)F)CC[C@@H](C4=CC=C(C=C4)F)O)O

IUPAC name: (3R,4S)-1-(4-fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-(4-hydroxyphenyl)azetidin-2-one

ChEBI definition: A β-lactam that is azetidin-2-one which is substituted at 1, 3, and 4 by p-fluorophenyl, 3-(p-fluorophenyl)-3-hydroxypropyl, and 4-hydroxyphenyl groups, respectively (the 3R,3’S,4S enantiomer).

Pharmacological roles (ChEBI): anticholesteremic drug, antilipemic drug.

Other ChEBI roles (chemical / environmental): antimetabolite.

Also known as: Ezetimiba, Ezetimibe, Ezetimibe component of k-924, Ezetimibe component of liptruzet, Ezetimibe component of nexlizet, Ezetimibe component of roszet, Ezetimibe component of vytorin, Ezetrol, MK0653, NSC-758923, SCH-58235, SCH58235

Patent coverage: 7,846 distinct patent families (29,509 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
NPC1L1	NPC1 like intracellular cholesterol transporter 1	Inhibition	6.66	2.7%	Q9UHC9

Broader ChEMBL bioactivity targets: 19 (assay-derived). Sample: Nuclear receptor ROR-gamma, Prelamin-A/C, NPC1-like intracellular cholesterol transporter 1, D(1A) dopamine receptor, Thromboxane A2 receptor, Progesterone receptor, Muscarinic acetylcholine receptor M1, Prostaglandin G/H synthase 1, Sodium-dependent noradrenaline transporter, Alpha-1A adrenergic receptor.

Bioactivity

ChEMBL activities: 10 potent at pChembl ≥ 5 of 21 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
LMNA	8.25	Potency	5.6	nM	CHEMBL_ACT_3641852
Q6T3U3	6.7	Ki	200	nM	CHEMBL_ACT_2093718
NPC1L1	6.43	IC50	370	nM	CHEMBL_ACT_24775578
CHRM1	5.34	AC50	4549	nM	CHEMBL_ACT_25209996
NPSR1	5.3	Potency	5012	nM	CHEMBL_ACT_4937223
ADORA3	5.2	AC50	6338	nM	CHEMBL_ACT_25198521
PTGS1	5.17	AC50	6718	nM	CHEMBL_ACT_25204977
P51450	5.15	Potency	7080	nM	CHEMBL_ACT_4971950
TBXA2R	5.12	AC50	7675	nM	CHEMBL_ACT_25197615
ADRA1A	5	AC50	9940	nM	CHEMBL_ACT_25208304

Target pathways

Aggregated over 1 target gene(s): NPC1L1.

Top Reactome pathways

1 total, by targets touching each:

Pathway	Targets	Genes
Intestinal lipid absorption	1	NPC1L1

Dominant GO biological processes

GO term	Targets
cholesterol biosynthetic process	1
sterol transport	1
intestinal cholesterol absorption	1
cholesterol transport	1
lipoprotein metabolic process	1
vitamin E metabolic process	1
cholesterol homeostasis	1
vitamin transport	1
cellular response to sterol depletion	1
lipid metabolic process	1
steroid metabolic process	1
cholesterol metabolic process	1
response to xenobiotic stimulus	1
response to muscle activity	1
cholesterol import	1

Indications & clinical

Indications

21 indications (5 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
familial hypercholesterolemia	4	MONDO:0005439	EFO:0004911
hyperlipidemia	4	MONDO:0021187	MONDO:0021187
metabolic syndrome X	3	MONDO:0011565	EFO:0000195
atherosclerosis	3	MONDO:0005311	EFO:0003914
hypertensive disorder	3	MONDO:0005044	EFO:0000537
hypertriglyceridemia	3	MONDO:0005347	EFO:0004211
diabetes mellitus	3	MONDO:0005015	EFO:0000400
myocardial infarction	3	MONDO:0005068	EFO:0000612
coronary artery disorder	3	MONDO:0005010	EFO:0001645
type 2 diabetes mellitus	3	MONDO:0005148	MONDO:0005148
inborn errors of metabolism	3	MONDO:0019052	MONDO:0019052
aortic valve stenosis	3	MONDO:0042981	HP:0001650
chronic hepatitis C virus infection	2	MONDO:0005354	EFO:0004220
metabolic dysfunction-associated steatotic liver disease	2	MONDO:0013209	EFO:0003095
hepatitis D virus infection	2	MONDO:0005789	EFO:0007304
HIV infectious disease	1	MONDO:0005109	EFO:0000764

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

Clinical trials

Total trials: 263.

Phase distribution

Phase	Trials
PHASE3	92
PHASE4	78
Not specified	38
PHASE2	27
PHASE1	24
EARLY_PHASE1	3
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05641753	PHASE4	RECRUITING	Cholesterol Lowering and Residual Risk in Diabetes, Type 1
NCT06767345	PHASE4	RECRUITING	Comparison of Moderate-Intensity Statin Plus Ezetimibe vs. High-Intensity Statin for Coronary Plaque Stabilization
NCT07255820	PHASE4	NOT_YET_RECRUITING	Dual vs Triple Lipid-Lowering Therapy in Type 2 Diabetes Mellitus Patients With Elevated LDL Cholesterol
NCT07442630	PHASE4	ACTIVE_NOT_RECRUITING	Long-term Comparison of Pitavastatin/Ezetimibe and Pitavastatin in Patients With Hypercholesterolemia and Elevated Triglycerides
NCT07508254	PHASE4	NOT_YET_RECRUITING	Triple vs Dual Lipid-Lowering Therapy for LDL-C Reduction in Acute Coronary Syndrome
NCT07605130	PHASE4	NOT_YET_RECRUITING	Efficacy and Safety Study of Digital Cognitive Training and PCSK9 Inhibitor-Enhanced Lipid-lowering Strategy in Patients With Intracranial Atherosclerotic Stenosis: A 2×2 Randomized Controlled Trial
NCT00079638	PHASE4	COMPLETED	Comparative Efficacy Evaluation of Lipids When Treated With Niaspan & Statin or Other Lipid-Modifying Therapies-COMPELL
NCT00125593	PHASE4	COMPLETED	Study of Heart and Renal Protection
NCT00185107	PHASE4	COMPLETED	Effect of Combination Therapy With Two Drugs (Colesevelam and Ezetimibe) in Patients With High Cholesterol
NCT00189085	PHASE4	COMPLETED	Effects of Ezetimibe on Postprandial Hyperlipidemia and Endothelial Function
NCT00202904	PHASE4	COMPLETED	Effectiveness and Safety of Ezetimibe Added to Atorvastatin in Patients With High Cholesterol and Coronary Heart Disease (Study P03740)
NCT00203476	PHASE4	COMPLETED	A Prospective, Open Label Comparison of Ezetimibe, Niacin, and Colestipol as Adjunct Therapy in Lipid Reduction
NCT00317993	PHASE4	COMPLETED	LDL Receptor Under Ezetimibe and Simvastatin
NCT00319449	PHASE4	COMPLETED	Adding Ezetimibe Tablet to Ongoing Treatment With Atorvastatin in Subjects With High Cholesterol and Multiple Coronary Heart Disease Risk Factors (Study P04060)(COMPLETED)
NCT00376246	PHASE4	COMPLETED	Effect of Ezetimibe on Flow-mediated Brachial Artery Reactivity in Healthy Subjects
NCT00385658	PHASE4	COMPLETED	Efficacy of Fluvastatin and Fenofibrate in Comparison to Simvastatin and Ezetimibe in Patients With Metabolic Syndrome
NCT00397657	PHASE4	TERMINATED	Comparative Study of the Effect of Ezetimibe Versus Extended-Release Niacin on Atherosclerosis
NCT00423579	PHASE4	COMPLETED	The Effects of Ezetimibe/Simvastatin 10/20 mg Versus Simvastatin 40 mg in High Cholesterol and Coronary Heart Disease Study (P04039AM2)(COMPLETED)
NCT00433823	PHASE4	UNKNOWN	A Study Evaluating the Effects of Lipid Lowering Treatment on Steroid Synthesis
NCT00449410	PHASE4	COMPLETED	Silent Cerebrovascular Lesion and Cognitive Decline Prevention by Cholesterol Lowering in Elderly AF Patients
NCT00466401	PHASE4	COMPLETED	Effect of Ezetimibe on Platelet Aggregation and LDL Tendency to Peroxidation
NCT00481351	PHASE4	COMPLETED	Effects of Statin and Ezetimibe Association on Kinetics of Artificial Chilomicrons
NCT00650663	PHASE4	COMPLETED	Ezetimibe Plus Simvastatin Versus Simvastatin Alone in African-American Subjects With Primary Hypercholesterolemia (P03377)
NCT00651014	PHASE4	TERMINATED	Ezetimibe Plus Simvastatin Versus Simvastatin in Patients With Hypercholesterolemia and Coronary Risk Factors (P03405)
NCT00651274	PHASE4	COMPLETED	Comparison of Co-administration of Ezetimibe Plus Simvastatin Versus Simvastatin Alone in Primary Hypercholesterolemia (P03476)
NCT00651378	PHASE4	TERMINATED	Switching to Rosuvastatin Versus Adding Ezetimibe to Atorvastatin Versus Doubling the Dose of Atorvastatin in Patients With Hypercholesterolemia and Risk Factors (P03708)
NCT00651963	PHASE4	COMPLETED	Open Label Study Evaluating The Use Of Combination Therapy Of Ezetimibe And Statins In Patients With Dyslipidemia In Colombia (0653-141)(COMPLETED)
NCT00652327	PHASE4	COMPLETED	Comparison of Ezetimibe Added to Ongoing Statin Therapy Versus Doubling the Dose of Statin in the Treatment of Hypercholesterolemia (P04355)
NCT00652444	PHASE4	COMPLETED	Effect Of Ezetimibe Coadministration With Simvastatin In A Middle Eastern Population: A Prospective, Multicentre, Randomized, Double-Blind, Placebo-Controlled Trial (0653-151)
NCT00652717	PHASE4	COMPLETED	Study To Assess The Efficacy Of A Cholesterol Lowering Drug On Top Of Statins In Patients After Myocardial Infarction (MI)(0653A-150)
NCT00652847	PHASE4	COMPLETED	Randomized Parallel Group Trial Of The Efficacy And Safety Of Ezetimibe With A Statin Versus Statin Dose Doubling In Patients With Persistent Primary Hypercholesterolemia (0653-152)(COMPLETED)
NCT00653796	PHASE4	COMPLETED	Ezetimibe Plus Atorvastatin Versus Atorvastatin in Untreated Subjects With High Cholesterol (P03434)
NCT00653835	PHASE4	COMPLETED	Ezetimibe Plus Simvastatin Versus Simvastatin in Untreated Subjects With High Cholesterol (P03435)
NCT00687076	PHASE4	COMPLETED	Effectiveness of Intensive Lipid Modification Medication in Preventing the Progression of Peripheral Arterial Disease (The ELIMIT Study)
NCT00699023	PHASE4	COMPLETED	Ezetimibe and Statins on Postprandial Lipemia in Type 2 Diabetes
NCT00701727	PHASE4	COMPLETED	Ezetimibe Reverse Cholesterol Transport (RCT) Pilot Study
NCT00753883	PHASE4	COMPLETED	Ezetrol Post-Marketing Study
NCT00794677	PHASE4	COMPLETED	Effects of Ezetimibe on the Absorption of Oxidized Cholesterol
NCT00817843	PHASE4	COMPLETED	The PostprAndial eNdothelial Function After Combination of Ezetimibe and simvAstatin Study
NCT00819403	PHASE4	COMPLETED	Simvastatin With or Without Ezetimibe and Atherothrombotic Biomarker Assessment

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 0 clinical and 5 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.

3 molecules share ≥1 primary target. Top 3 by shared-target count:

Molecule	Source	Status	Shared targets
Cholesterol	PubChem	Approved	NPC1L1
Orlistat	PubChem	Approved	NPC1L1
prasterone	PubChem	Approved	NPC1L1