General
Preferred name
ezetimibe
Synonyms
Ezetimibe D4 ()
SCH 58235 D4 ()
SCH 58235 ()
Ezetimibe (Zetia) ()
Vytorin-ezetimibe ()
Ezetimibe (SCH-58235) ()
SCH-58235 ()
SCH58235 ()
Ezetrol ()
MK0653 ()
Zetia ()
NSC-758923 ()
Ezetimibe-d4 ()
P&D ID
PD002999
CAS
163222-33-1
1093659-89-2
Tags
natural product
drug
available
Approved by
PMDA
FDA
First approval
2002
Drug Status
approved
Drug indication
Hypercholesterolaemia
Max Phase
Phase 4
Structure
Probe scores
P&D probe-likeness score
[[ v.score ]]%
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
MOA Ezetimibe mediates its blood cholesterol-lowering effect via selectively inhibiting the absorption of cholesterol and phytosterol by the small intestine without altering the absorption of fat-soluble vitamins and nutrients [A15202]. The primary target of ezetimibe is the cholesterol transport protein Niemann-Pick C1-Like 1 (NPC1L1) protein. NPC1L1 is expressed at the enterocyte/ gut lumen (apical) as well as the hepatobiliary (canalicular) interface and plays a role in facilitating internalization of free cholesterol into the enterocyte in conjunction with the adaptor protein 2 (AP2) complex and clathrin [A33309]. Once cholesterol in the gut lumen or bile is incorporated into the cell membrane of enterocytes, it can bind to the sterol-sensing domain of NPC1L1 and form a NPC1L1/cholesterol complex. The complex can then be internalized or endocytosed by joining to AP2 clathrin, forming a vesicle complex that is translocated for storage in the endocytic recycling compartment [A33309]. ; ; Ezetimibe does not require exocrine pancreatic function for its pharmacological activity; rather, it localizes and appears to act at the brush border of the small intestine. Ezetimibe selectively blocks the NPC1L1 protein in the jejunal brush border, reducing the uptake of intestinal lumen micelles into the enterocyte [A33309]. Overall, ezetimibe causes a decrease in the delivery of intestinal cholesterol to the liver and reduction of hepatic cholesterol stores and an increase in clearance of cholesterol from the blood. While the full mechanism of action of ezetimibe in reducing the entry of cholesterol into both enterocytes and hepatocytes is not fully understood, a study proposed that ezetimibe prevents the NPC1L1/sterol complex from interacting with AP2 in clathrin coated vesicles and induces a conformational change in NPC1L1, rendering it incapable of binding to sterols [A33309]. Another study suggested that ezetimibe disrupts the function of other proteins complexes involved in regulating cholesterol uptake, including the CAV1– annexin 2 heterocomplex [A33309].
DESCRIPTION Inhibits the intestinal cholesterol uptake protein Niemann-Pick C1-like protein 1 (NPC1L1). Analysis of cryo-EM structures reveals how NPC1L1 transports cholesterol and the mechanism of ezetimibe inhibition . (GtoPdb)
Cell lines
0
Organisms
5
Compound Sets
32
AdooQ Bioactive Compound Library
A10379
Axon Medchem Screening Library
3377
Cayman Chemical Bioactives
16331
25044
CeMM library of unique drugs (CLOUD)
ChEMBL Approved Drugs
CHEMBL1138
ChEMBL Drugs
CHEMBL1138
Concise Guide to Pharmacology 2017/18
6816
Concise Guide to Pharmacology 2019/20
6816
Concise Guide to Pharmacology 2021/22
6816
Concise Guide to Pharmacology 2023/24
6816
Drug Repurposing Hub
DrugBank
DB00973
DrugBank Approved Drugs
DB00973
DrugCentral
1125
DrugCentral Approved Drugs
1125
DrugMAP
DM7A8TW
DrugMAP Approved Drugs
DM7A8TW
Enamine BioReference Compounds
EU-OPENSCREEN Bioactive Compound Library
EOS100005
Guide to Pharmacology
6816
MedChem Express Bioactive Compound Library
HY-17376
Natural product-based probes and drugs
NCATS Inxight Approved Drugs
EOR26LQQ24
NIH Clinical Collections (NCC)
Novartis Chemogenetic Library (NIBR MoA Box)
NPC Screening Collection
Other bioactive compounds
Pandemic Response Box
Prestwick Chemical Library
ReFrame library
Selleckchem Bioactive Compound Library
Ezetimibe(Zetia)
TargetMol Bioactive Compound Library
T1593
External IDs
50
Properties
(calculated by RDKit )
Molecular Weight
409.15
Hydrogen Bond Acceptors
3
Hydrogen Bond Donors
2
Rotatable Bonds
6
Ring Count
4
Aromatic Ring Count
3
cLogP
4.89
TPSA
60.77
Fraction CSP3
0.21
Chiral centers
3.0
Largest ring
6.0
QED
0.57
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Pathway
NF-¦ÊB
Immunology/Inflammation
Membrane Transporter/Ion Channel
NF-??
Autophagy
NF-κB
MOA
Niemann-Pick C1-Like 1 protein inhibitor
Niemann-Pick C1-like protein 1 (NPC1L1) Inhibitors
Cholesterol Absorption Inhibitors
cholesterol inhibitor, Niemann-Pick C1-like 1 protein antagonist
Target
Niemann-Pick C1-like protein 1
NPC1L1
Nrf2
Sterol O-acyltransferase
ANPEP, NPC1L1, SOAT1
Cholesterol absorption inhibitor
Keap1-Nrf2
LDL
Member status
member
Indication
hyperlipidemia, hypercholesterolemia, sitosterolemia
Disease Area
endocrinology, metabolism
Therapeutic Indication
Hypocholesterolemic
Therapeutic Class
Cardiovascular
Anticholesteremic Agents
Source data