Ezetimibe
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Identification
- Summary
Ezetimibe is a cholesterol absorption inhibitor used to lower total cholesterol, LDL-C, Apo-B, and non-HDL-C in primary hyperlipidemia and familial cholesterolemia.
- Brand Names
- Ezetrol, Lypqozet, Nexlizet, Roszet, Vytorin, Zetia
- Generic Name
- Ezetimibe
- DrugBank Accession Number
- DB00973
- Background
Ezetimibe is a lipid-lowering compound that inhibits intestinal cholesterol and phytosterol absorption. The discovery and research of this drug began in the early 1990s, after the intravenous administration of radiolabelled ezetimibe in rats revealed that it was being localized within enterocytes of the intestinal villi - this prompted studies investigating the effect of ezetimibe on intestinal cholesterol absorption.3 Ezetimibe is used as an adjunctive therapy to a healthy diet to lower cholesterol levels in primary hyperlipidemia, mixed hyperlipidemia, homozygous familial hypercholesterolemia (HoFH), and homozygous sitosterolemia (phytosterolemia).5
Unlike other classes of cholesterol-reducing compounds including statins and bile acid sequestrants, ezetimibe has a distinct mechanism of action involving the sterol transporter Niemann-Pick C1-Like 1 (NPC1L1), and is unique in that it does not affect the absorption of fat-soluble nutrients such as fat-soluble vitamins, triglycerides, or bile acids.4 In genetically NPC1L1-deficient mice, a 70% reduction in intestinal cholesterol absorption was seen, and these mice were insensitive to ezetimibe treatment - it was determined based on these findings that NPC1L1 plays an essential role in promoting intestinal cholesterol uptake via an ezetimibe-sensitive pathway.3 By interfering with the intestinal uptake of cholesterol and phytosterols, ezetimibe reduces the delivery of intestinal cholesterol to the liver.5
- Type
- Small Molecule
- Groups
- Approved
- Structure
- Weight
- Average: 409.4252
Monoisotopic: 409.148949953 - Chemical Formula
- C24H21F2NO3
- Synonyms
- Ezetimiba
- ézétimibe
- Ezetimibe
- Ezetimibum
- External IDs
- MK0653
- SCH 58235
- SCH-58235
- SCH58235
Pharmacology
- Indication
Ezetimibe is indicated to reduce elevated total-C, LDL-C, Apo B, and non-HDL-C in patients with primary hyperlipidemia, alone or in combination with an HMG-CoA reductase inhibitor (statin).5,6,7
It is also indicated to reduce elevated total-C, LDL-C, Apo B, and non-HDL-C in patients with mixed hyperlipidemia in combination with fenofibrate, and to reduce elevated total-C and LDL-C in patients with homozygous familial hypercholesterolemia (HoFH) in combination with atorvastatin or simvastatin.5 In combination with bempedoic acid, ezetimibe is indicated as an adjunct to diet, with or without other lipid-lowering therapies, to reduce LDL-C in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH).10
Ezetimibe may also be used to reduce elevated sitosterol and campesterol in patients with homozygous sitosterolemia (phytosterolemia).5
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used as adjunct in combination to manage Elevated blood lipids Regimen in combination with: Simvastatin (DB00641) •••••••••••• •••••• Used as adjunct in combination to manage Elevated blood lipids Regimen in combination with: Atorvastatin (DB01076) •••••••••••• •••••• Used as adjunct in combination to manage Elevated blood lipids Regimen in combination with: Fenofibrate (DB01039) •••••••••••• •••••• Used as adjunct in combination to manage Elevated blood lipids •••••••••••• •••••• Adjunct therapy in management of Elevated blood lipids •••••••••••• •••••• - Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- Pharmacodynamics
Ezetimibe was shown to reduce the levels of total cholesterol (total-C), low-density lipoprotein cholesterol (LDL-C), apoprotein B (Apo B), non-high-density lipoprotein cholesterol (non-HDL-C), and triglycerides (TG), and increase high-density lipoprotein cholesterol (HDL-C) in patients with hyperlipidemia.5 This therapeutic effect was more profound when ezetimibe was co-administered with a statin or fenofibrate compared to either treatment alone.5 In clinical trials involving patients with homozygous and heterozygous familial hypercholesterolemia and in those with sitosterolemia, a recommended therapeutic dose of ezetimibe was effective in reducing the LDL levels by 15-20% while increasing HDL-C by 2.5-5%.4
The effects of increased exposure to ezetimibe secondary to moderate-severe hepatic impairment have not been assessed - patients meeting these criteria should avoid the use of ezetimibe.5 Post-marketing reports indicate the potential for myopathy and rhabdomyolysis in patients taking ezetimibe, and this risk appears to be exacerbated in patients concurrently receiving, or having recently received, statin therapy.5
- Mechanism of action
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.3 The primary target of ezetimibe is the cholesterol transport protein Niemann-Pick C1-Like 1 (NPC1L1) protein. NPC1L1 is expressed on enterocytes/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.2 Once cholesterol in the gut lumen or bile is incorporated into the cell membrane of enterocytes, it binds to the sterol-sensing domain of NPC1L1 and forms a NPC1L1/cholesterol complex. The complex is then internalized or endocytosed by joining to AP2 clathrin, forming a vesicle complex that is translocated for storage in the endocytic recycling compartment.2
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.2 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, one 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.2 Another study suggested that ezetimibe disrupts the function of other protein complexes involved in regulating cholesterol uptake, including the CAV1–annexin 2 heterocomplex.2
Target Actions Organism ANPC1-like intracellular cholesterol transporter 1 inhibitorHumans ASterol O-acyltransferase 1 inhibitorHumans UAminopeptidase N otherHumans - Absorption
Administration of a single 10-mg dose of ezetimibe in fasted adults resulted in peak plasma concentrations (Cmax) of 3.4-5.5 ng/mL within 4-12 hours (Tmax).5 The Cmax of the major pharmacologically-active metabolite, ezetimibe-glucuronide, was 45-71 ng/mL and its Tmax was 1-2 hours.5 Food consumption has minimal effect on ezetimibe absorption, but the Cmax is increased by 38% when administered alongside a high-fat meal.5 The true bioavailability of ezetimibe cannot be determined, as it is insoluble in aqueous media suitable for intravenous injection.5
- Volume of distribution
The relative volume of distribution of ezetimibe is 107.5L.11
- Protein binding
Ezetimibe and ezetimibe-glucuronide are >90% bound to human plasma proteins.5 The mean in vitro protein binding ranged from 99.5% to 99.8% for ezetimibe and 87.8% to 92.0% for ezetimibe-glucuronide.3
- Metabolism
In humans, ezetimibe is rapidly and extensively metabolized via a phase II glucuronide conjugation reaction in the small intestine and liver to form its main phenolic metabolite, ezetimibe glucuronide. The main human liver and/or intestinal uridine 5′-diphosphate (UDP)-glucuronosyltransferase (UGT) enzymes responsible for the glucuronidation of ezetimibe were shown to be UGT1A1, 1A3, and 2B15 in vitro.3 Minimal phase I reaction involving oxidation of ezetimibe also occurs to form SCH 57871, and human jejunum microsomes also produced trace levels of a benzylic glucuronide (SCH 488128).3 Ezetimibe glucuronide accounts for 80-90% of the total circulating compound in plasma, and retains some pharmacological activity in inhibiting intestinal cholesterol uptake.5 In humans, ezetimibe and ezetimibe-glucuronide constitutes approximately 93% of the total drug in plasma.5 Plasma concentration-time profiles exhibit multiple peaks, suggestive of enterohepatic recycling5, and about 20% of the drug distributed is reabsorbed due to enterohepatic recirculation.11
Hover over products below to view reaction partners
- Route of elimination
Approximately 78% and 11% of orally administered radiolabelled ezetimibe are recovered in the feces and urine, respectively.5 Unchanged parent drug is the major component in feces and accounts for approximately 69% of an administered dose, while ezetimibe-glucuronide is the major component in urine and accounts for approximately 9% of an administered dose.5 High recovery of unchanged parent drug in feces suggests low absorption and/or hydrolysis of ezetimibe-glucuronide secreted in the bile.3
- Half-life
Both ezetimibe and ezetimibe-glucuronide display an approximate half-life of 22 hours.5
- Clearance
There are no pharmacokinetic data available on the clearance of ezetimibe.
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Oral LD50 and intraperitoneal LD50 in rat were >2000 mg/kg.9 Estimated oral LD50 values in mouse and dog are >5000 mg/kg and >3000 mg/kg, respectively.9 One case of accidental overdose occurred in clinical studies in one female patient with homozygous sitosterolemia receiving 120 mg/day for 28 days with no reported clinical or laboratory adverse events.5 In case of overdose, symptomatic treatment is recommended.5
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbemaciclib Abemaciclib may decrease the excretion rate of Ezetimibe which could result in a higher serum level. Acetylcysteine The excretion of Ezetimibe can be decreased when combined with Acetylcysteine. Adenine The metabolism of Ezetimibe can be decreased when combined with Adenine. Afatinib Afatinib may decrease the excretion rate of Ezetimibe which could result in a higher serum level. Alectinib Alectinib may decrease the excretion rate of Ezetimibe which could result in a higher serum level. - Food Interactions
- Take with or without food. Co-administration with food does not affect absorption.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Product Images
- International/Other Brands
- Ezedoc / Ezetib / Zient
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Act Ezetimibe Tablet 10 mg Oral Actavis Pharma Company 2014-09-15 2018-06-12 Canada Ezetimibe Tablet 10 mg Oral Laboratoire Riva Inc. 2018-08-14 Not applicable Canada Ezetimibe Tablet 10 mg Oral Sivem Pharmaceuticals Ulc 2014-09-16 Not applicable Canada Ezetimibe Tablet 10 mg Oral Pro Doc Limitee 2014-09-17 Not applicable Canada Ezetimibe Tablet 10 mg Oral Sanis Health Inc 2014-10-08 Not applicable Canada - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Ach-ezetimibe Tablet 10 mg Oral Accord Healthcare, S.L.U. 2014-09-17 Not applicable Canada Ag-ezetimibe Tablet 10 mg Oral Angita Pharma Inc. 2018-07-20 Not applicable Canada Apo-ezetimibe Tablet 10 mg Oral Apotex Corporation 2014-09-23 Not applicable Canada Auro-ezetimibe Tablet 10 mg Oral Auro Pharma Inc 2018-04-25 Not applicable Canada Bio-ezetimibe Tablet 10 mg Oral Biomed Pharma 2014-10-08 Not applicable Canada - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image AMISITELA Ezetimibe (10 MG) + Simvastatin (10 MG) Tablet Oral Pharmacare S.R.L. 2019-10-10 Not applicable Italy AMISITELA Ezetimibe (10 MG) + Simvastatin (20 MG) Tablet Oral Pharmacare S.R.L. 2019-10-10 Not applicable Italy AMISITELA Ezetimibe (10 MG) + Simvastatin (40 MG) Tablet Oral Pharmacare S.R.L. 2019-10-10 Not applicable Italy Arosuva plus Ezetimib 10 mg/10 mg Filmtabletten Ezetimibe (10 mg) + Rosuvastatin (10 mg) Tablet, film coated Oral Gebro Pharma Gmb H 2019-11-04 Not applicable Austria Arosuva plus Ezetimib 20 mg/10 mg Filmtabletten Ezetimibe (10 mg) + Rosuvastatin (20 mg) Tablet, film coated Oral Gebro Pharma Gmb H 2019-11-04 Not applicable Austria
Categories
- ATC Codes
- C10BA02 — Simvastatin and ezetimibe
- C10BA — Combinations of various lipid modifying agents
- C10B — LIPID MODIFYING AGENTS, COMBINATIONS
- C10 — LIPID MODIFYING AGENTS
- C — CARDIOVASCULAR SYSTEM
- C10BA — Combinations of various lipid modifying agents
- C10B — LIPID MODIFYING AGENTS, COMBINATIONS
- C10 — LIPID MODIFYING AGENTS
- C — CARDIOVASCULAR SYSTEM
- C10BA — Combinations of various lipid modifying agents
- C10B — LIPID MODIFYING AGENTS, COMBINATIONS
- C10 — LIPID MODIFYING AGENTS
- C — CARDIOVASCULAR SYSTEM
- C10BA — Combinations of various lipid modifying agents
- C10B — LIPID MODIFYING AGENTS, COMBINATIONS
- C10 — LIPID MODIFYING AGENTS
- C — CARDIOVASCULAR SYSTEM
- C10BA — Combinations of various lipid modifying agents
- C10B — LIPID MODIFYING AGENTS, COMBINATIONS
- C10 — LIPID MODIFYING AGENTS
- C — CARDIOVASCULAR SYSTEM
- C10AX — Other lipid modifying agents
- C10A — LIPID MODIFYING AGENTS, PLAIN
- C10 — LIPID MODIFYING AGENTS
- C — CARDIOVASCULAR SYSTEM
- Drug Categories
- Anticholesteremic Agents
- Azetines
- BCRP/ABCG2 Substrates
- BSEP/ABCB11 Substrates
- Cytochrome P-450 CYP2C8 Inhibitors
- Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)
- Cytochrome P-450 Enzyme Inhibitors
- Decreased Cholesterol Absorption
- Dietary Cholesterol Absorption Inhibitor
- Hypolipidemic Agents
- Hypolipidemic Agents Indicated for Hyperlipidemia
- Lipid Modifying Agents
- Lipid Modifying Agents, Plain
- Lipid Regulating Agents
- Non-statin Hypolipidemic Agents Indicated for Hyperlipidemia
- OATP1B1/SLCO1B1 Substrates
- P-glycoprotein substrates
- UGT1A1 Substrates
- UGT1A3 substrates
- UGT2B7 substrates
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as monobactams. These are compounds comprising beta-lactam ring is alone and not fused to another ring.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Lactams
- Sub Class
- Beta lactams
- Direct Parent
- Monobactams
- Alternative Parents
- Phenylazetidines / Fluorobenzenes / 1-hydroxy-2-unsubstituted benzenoids / Aryl fluorides / Tertiary carboxylic acid amides / Secondary alcohols / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organofluorides show 4 more
- Substituents
- 1-hydroxy-2-unsubstituted benzenoid / 1-phenylazetidine / 2-phenylazetidine / Alcohol / Aromatic alcohol / Aromatic heteromonocyclic compound / Aryl fluoride / Aryl halide / Azacycle / Azetidine show 20 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- organofluorine compound, azetidines, beta-lactam (CHEBI:49040)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- EOR26LQQ24
- CAS number
- 163222-33-1
- InChI Key
- OLNTVTPDXPETLC-XPWALMASSA-N
- InChI
- InChI=1S/C24H21F2NO3/c25-17-5-1-15(2-6-17)22(29)14-13-21-23(16-3-11-20(28)12-4-16)27(24(21)30)19-9-7-18(26)8-10-19/h1-12,21-23,28-29H,13-14H2/t21-,22+,23-/m1/s1
- IUPAC Name
- (3R,4S)-1-(4-fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-(4-hydroxyphenyl)azetidin-2-one
- SMILES
- [H][C@]1(CC[C@H](O)C2=CC=C(F)C=C2)C(=O)N(C2=CC=C(F)C=C2)[C@]1([H])C1=CC=C(O)C=C1
References
- Synthesis Reference
Venkataraman Sundaram, Srinivasam Rajan, Vaddadi Ramayya, Sunkara Vardhan, Bulusu Subrahmanyam, Cheemalapati Sasikala, "Polymorphs of ezetimibe and process for preparation thereof." U.S. Patent US20050171080, issued August 04, 2005.
US20050171080- General References
- Garcia-Calvo M, Lisnock J, Bull HG, Hawes BE, Burnett DA, Braun MP, Crona JH, Davis HR Jr, Dean DC, Detmers PA, Graziano MP, Hughes M, Macintyre DE, Ogawa A, O'neill KA, Iyer SP, Shevell DE, Smith MM, Tang YS, Makarewicz AM, Ujjainwalla F, Altmann SW, Chapman KT, Thornberry NA: The target of ezetimibe is Niemann-Pick C1-Like 1 (NPC1L1). Proc Natl Acad Sci U S A. 2005 Jun 7;102(23):8132-7. Epub 2005 May 31. [Article]
- Phan BA, Dayspring TD, Toth PP: Ezetimibe therapy: mechanism of action and clinical update. Vasc Health Risk Manag. 2012;8:415-27. doi: 10.2147/VHRM.S33664. Epub 2012 Jul 3. [Article]
- Kosoglou T, Statkevich P, Johnson-Levonas AO, Paolini JF, Bergman AJ, Alton KB: Ezetimibe: a review of its metabolism, pharmacokinetics and drug interactions. Clin Pharmacokinet. 2005;44(5):467-94. [Article]
- Nutescu EA, Shapiro NL: Ezetimibe: a selective cholesterol absorption inhibitor. Pharmacotherapy. 2003 Nov;23(11):1463-74. [Article]
- FDA Approved Drug Products: Zetia (ezetimibe) oral tablets [Link]
- FDA Approved Drug Products: Liptruzet (ezetimibe/atorvastatin) oral tablets [Link]
- FDA Approved Drug Products: Vytorin (ezetimibe/simvastatin) oral tablets [Link]
- CaymanChem: Ezetimibe MSDS [Link]
- Health Canada Product Monograph: Ezetimibe oral tablets [Link]
- FDA Approved Products: Nexlizet (bempedoic acid and ezetimibe) oral tablets [Link]
- Getz Pharma: Ezita (Ezetimibe 10mg tablets) Product Label [File]
- External Links
- Human Metabolome Database
- HMDB0015108
- KEGG Drug
- D01966
- PubChem Compound
- 150311
- PubChem Substance
- 46507625
- ChemSpider
- 132493
- BindingDB
- 50371521
- 341248
- ChEBI
- 49040
- ChEMBL
- CHEMBL1138
- ZINC
- ZINC000003810860
- Therapeutic Targets Database
- DAP000717
- PharmGKB
- PA10816
- PDBe Ligand
- H56
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Ezetimibe
- PDB Entries
- 7dfz / 8axw
- FDA label
- Download (350 KB)
- MSDS
- Download (281 KB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Active Not Recruiting Not Available Dyslipidemia 2 somestatus stop reason just information to hide Not Available Active Not Recruiting Not Available Dyslipoproteinemias 1 somestatus stop reason just information to hide Not Available Active Not Recruiting Treatment Coronavirus Disease 2019 (COVID‑19) / Non ST Segment Elevation Myocardial Infarction (NSTEMI) / ST Segment Elevation Myocardial Infarction (STEMI) 1 somestatus stop reason just information to hide Not Available Completed Not Available Atherosclerotic Cardiovascular Diseases 1 somestatus stop reason just information to hide Not Available Completed Not Available Breastfeeding 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Msp singapore co llc
- Packagers
- AQ Pharmaceuticals Inc.
- A-S Medication Solutions LLC
- Cardinal Health
- Diversified Healthcare Services Inc.
- Lake Erie Medical and Surgical Supply
- Merck & Co.
- MSP Distribution Services LLC
- PD-Rx Pharmaceuticals Inc.
- Physicians Total Care Inc.
- Prepackage Specialists
- Prepak Systems Inc.
- Quality Care
- Resource Optimization and Innovation LLC
- Schering-Plough Inc.
- Vangard Labs Inc.
- Dosage Forms
Form Route Strength Tablet Oral 10.000 mg Tablet Oral 10.00 mg Tablet Oral 20.800 mg Tablet, coated Oral Tablet, film coated Oral 10 mg Tablet Oral Capsule, liquid filled Oral Capsule Oral Tablet, film coated Oral Tablet Oral 10.00 mg Tablet Oral 10.000 mg Tablet Oral 86.800 mg Tablet Oral Tablet Oral 10 mg/1 Tablet Oral 10 mg - Prices
Unit description Cost Unit Zetia 10 mg tablet 5.15USD tablet DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US5846966 No 1998-12-08 2013-09-21 US US5969156 Yes 1999-10-19 2017-01-08 US USRE37721 Yes 2002-05-28 2017-04-25 US USRE42461 Yes 2011-06-14 2017-04-25 US US7612058 Yes 2009-11-03 2026-04-30 US US7030106 Yes 2006-04-18 2022-07-25 US US7335799 No 2008-02-26 2025-12-03 US US9624152 No 2017-04-18 2023-12-23 US US8497301 No 2013-07-30 2023-12-23 US US9000041 No 2015-04-07 2023-12-23 US US10118881 No 2018-11-06 2023-12-23 US US10941095 No 2021-03-09 2023-12-23 US US10376470 No 2019-08-13 2033-05-01 US US9763885 No 2017-09-19 2033-05-01 US US10912751 No 2021-02-09 2036-03-14 US US11613511 No 2020-06-19 2040-06-19 US US11744816 No 2016-03-14 2036-03-14 US US11760714 No 2020-06-19 2040-06-19 US US11926584 No 2020-06-19 2040-06-19 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 163°C FDA label water solubility Practically insoluble FDA label - Predicted Properties
Property Value Source Water Solubility 0.00846 mg/mL ALOGPS logP 4.14 ALOGPS logP 4.56 Chemaxon logS -4.7 ALOGPS pKa (Strongest Acidic) 9.48 Chemaxon pKa (Strongest Basic) -3 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 60.77 Å2 Chemaxon Rotatable Bond Count 6 Chemaxon Refractivity 108.86 m3·mol-1 Chemaxon Polarizability 41.65 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9899 Blood Brain Barrier + 0.9074 Caco-2 permeable - 0.5225 P-glycoprotein substrate Non-substrate 0.6918 P-glycoprotein inhibitor I Non-inhibitor 0.6026 P-glycoprotein inhibitor II Inhibitor 0.5306 Renal organic cation transporter Non-inhibitor 0.8659 CYP450 2C9 substrate Non-substrate 0.8244 CYP450 2D6 substrate Non-substrate 0.7505 CYP450 3A4 substrate Substrate 0.5341 CYP450 1A2 substrate Non-inhibitor 0.7013 CYP450 2C9 inhibitor Non-inhibitor 0.6125 CYP450 2D6 inhibitor Non-inhibitor 0.8442 CYP450 2C19 inhibitor Non-inhibitor 0.5807 CYP450 3A4 inhibitor Inhibitor 0.796 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.5289 Ames test Non AMES toxic 0.7476 Carcinogenicity Non-carcinogens 0.8328 Biodegradation Not ready biodegradable 0.9853 Rat acute toxicity 2.4979 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9767 hERG inhibition (predictor II) Inhibitor 0.5455
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 216.5290497 predictedDarkChem Lite v0.1.0 [M-H]- 199.29549 predictedDeepCCS 1.0 (2019) [M+H]+ 217.2324497 predictedDarkChem Lite v0.1.0 [M+H]+ 201.69106 predictedDeepCCS 1.0 (2019) [M+Na]+ 216.1175497 predictedDarkChem Lite v0.1.0 [M+Na]+ 207.60358 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Plays a major role in cholesterol homeostasis (PubMed:22095670). Critical for the uptake of cholesterol across the plasma membrane of the intestinal enterocyte (PubMed:22095670). Involved in plant sterol absorption, it transports sitosterol, although at lower rates than cholesterol (By similarity). Is the direct molecular target of ezetimibe, a drug that inhibits cholesterol absorption and is approved for the treatment of hypercholesterolemia (PubMed:15928087). May have a function in the transport of multiple lipids and their homeostasis, thereby influencing lipid metabolism regulation (PubMed:15671032). May be involved in caveolin trafficking from the plasma membrane (By similarity). In addition, acts as a negative regulator of NPC2 and down-regulates its expression and secretion by inhibiting its maturation and accelerating its degradation (PubMed:22095670)
- Specific Function
- cholesterol binding
- Gene Name
- NPC1L1
- Uniprot ID
- Q9UHC9
- Uniprot Name
- NPC1-like intracellular cholesterol transporter 1
- Molecular Weight
- 148726.52 Da
References
- Altmann SW, Davis HR Jr, Zhu LJ, Yao X, Hoos LM, Tetzloff G, Iyer SP, Maguire M, Golovko A, Zeng M, Wang L, Murgolo N, Graziano MP: Niemann-Pick C1 Like 1 protein is critical for intestinal cholesterol absorption. Science. 2004 Feb 20;303(5661):1201-4. [Article]
- Wang J, Williams CM, Hegele RA: Compound heterozygosity for two non-synonymous polymorphisms in NPC1L1 in a non-responder to ezetimibe. Clin Genet. 2005 Feb;67(2):175-7. [Article]
- Sudhop T, Lutjohann D, von Bergmann K: Sterol transporters: targets of natural sterols and new lipid lowering drugs. Pharmacol Ther. 2005 Mar;105(3):333-41. Epub 2004 Dec 9. [Article]
- Garcia-Calvo M, Lisnock J, Bull HG, Hawes BE, Burnett DA, Braun MP, Crona JH, Davis HR Jr, Dean DC, Detmers PA, Graziano MP, Hughes M, Macintyre DE, Ogawa A, O'neill KA, Iyer SP, Shevell DE, Smith MM, Tang YS, Makarewicz AM, Ujjainwalla F, Altmann SW, Chapman KT, Thornberry NA: The target of ezetimibe is Niemann-Pick C1-Like 1 (NPC1L1). Proc Natl Acad Sci U S A. 2005 Jun 7;102(23):8132-7. Epub 2005 May 31. [Article]
- von Bergmann K, Sudhop T, Lutjohann D: Cholesterol and plant sterol absorption: recent insights. Am J Cardiol. 2005 Jul 4;96(1A):10D-14D. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Catalyzes the formation of fatty acid-cholesterol esters, which are less soluble in membranes than cholesterol (PubMed:16154994, PubMed:16647063, PubMed:32433613, PubMed:32433614, PubMed:32944968, PubMed:9020103). Plays a role in lipoprotein assembly and dietary cholesterol absorption (PubMed:16154994, PubMed:9020103). Preferentially utilizes oleoyl-CoA ((9Z)-octadecenoyl-CoA) as a substrate: shows a higher activity towards an acyl-CoA substrate with a double bond at the delta-9 position (9Z) than towards saturated acyl-CoA or an unsaturated acyl-CoA with a double bond at the delta-7 (7Z) or delta-11 (11Z) positions (PubMed:11294643, PubMed:32433614)
- Specific Function
- cholesterol binding
- Gene Name
- SOAT1
- Uniprot ID
- P35610
- Uniprot Name
- Sterol O-acyltransferase 1
- Molecular Weight
- 64733.975 Da
References
- Singh A, Basit A, Banerjee UC: Burkholderia cenocepacia: a new biocatalyst for efficient bioreduction of ezetimibe intermediate. J Ind Microbiol Biotechnol. 2009 Nov;36(11):1369-74. doi: 10.1007/s10295-009-0622-z. Epub 2009 Aug 8. [Article]
- Costet P: Molecular pathways and agents for lowering LDL-cholesterol in addition to statins. Pharmacol Ther. 2010 Jun;126(3):263-78. doi: 10.1016/j.pharmthera.2010.02.006. Epub 2010 Mar 19. [Article]
- Wang HH, Portincasa P, Mendez-Sanchez N, Uribe M, Wang DQ: Effect of ezetimibe on the prevention and dissolution of cholesterol gallstones. Gastroenterology. 2008 Jun;134(7):2101-10. doi: 10.1053/j.gastro.2008.03.011. Epub 2008 Mar 10. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Other
- General Function
- Broad specificity aminopeptidase which plays a role in the final digestion of peptides generated from hydrolysis of proteins by gastric and pancreatic proteases. Also involved in the processing of various peptides including peptide hormones, such as angiotensin III and IV, neuropeptides, and chemokines. May also be involved the cleavage of peptides bound to major histocompatibility complex class II molecules of antigen presenting cells. May have a role in angiogenesis and promote cholesterol crystallization. May have a role in amino acid transport by acting as binding partner of amino acid transporter SLC6A19 and regulating its activity (By similarity)
- Specific Function
- aminopeptidase activity
- Gene Name
- ANPEP
- Uniprot ID
- P15144
- Uniprot Name
- Aminopeptidase N
- Molecular Weight
- 109538.68 Da
References
- Kramer W, Girbig F, Corsiero D, Pfenninger A, Frick W, Jahne G, Rhein M, Wendler W, Lottspeich F, Hochleitner EO, Orso E, Schmitz G: Aminopeptidase N (CD13) is a molecular target of the cholesterol absorption inhibitor ezetimibe in the enterocyte brush border membrane. J Biol Chem. 2005 Jan 14;280(2):1306-20. Epub 2004 Oct 19. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:15472229, PubMed:18674515, PubMed:18719240, PubMed:23288867, PubMed:23756265, PubMed:24641623). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:23756265). Catalyzes the glucuronidation of endogenous estrogen hormones such as estradiol and estrone (PubMed:15472229, PubMed:18719240, PubMed:23288867). Contributes to bile acid (BA) detoxification by catalyzing the glucuronidation of BA substrates, which are natural detergents for dietary lipids absorption (PubMed:23756265). Involved in the glucuronidation of calcidiol, which is the major circulating form of vitamin D3, essential for the regulation of calcium and phosphate homeostasis (PubMed:24641623). Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonists losartan, candesartan and zolarsartan, which can inhibit the effect of angiotensin II (PubMed:18674515)
- Specific Function
- enzyme binding
- Gene Name
- UGT1A3
- Uniprot ID
- P35503
- Uniprot Name
- UDP-glucuronosyltransferase 1A3
- Molecular Weight
- 60337.835 Da
References
- Oswald S, Nassif A, Modess C, Keiser M, Ulrich A, Runge D, Hanke U, Lutjohann D, Engel A, Weitschies W, Siegmund W: Drug interactions between the immunosuppressant tacrolimus and the cholesterol absorption inhibitor ezetimibe in healthy volunteers. Clin Pharmacol Ther. 2011 Apr;89(4):524-8. doi: 10.1038/clpt.2011.4. Epub 2011 Mar 2. [Article]
- Kosoglou T, Statkevich P, Johnson-Levonas AO, Paolini JF, Bergman AJ, Alton KB: Ezetimibe: a review of its metabolism, pharmacokinetics and drug interactions. Clin Pharmacokinet. 2005;44(5):467-94. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:16595710, PubMed:18719240, PubMed:23288867, PubMed:7835232, PubMed:9295060). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:7835232). Catalyzes the glucuronidation of endogenous steroid hormones such as androgens (testosterone, androsterone) and estrogens (estradiol, epiestradiol, estriol, catechol estrogens) (PubMed:16595710, PubMed:18719240, PubMed:23288867, PubMed:7835232, PubMed:9295060). Displays glucuronidation activity toward several classes of xenobiotic substrates, including phenolic compounds (eugenol, 4-nitrophenol, 4-hydroxybiphenyl) and phenylpropanoids (naringenin, coumarins) (PubMed:7835232). Catalyzes the glucuronidation of monoterpenoid alcohols such as borneol, menthol and isomenthol, a class of natural compounds used in essential oils (By similarity)
- Specific Function
- glucuronosyltransferase activity
- Gene Name
- UGT2B15
- Uniprot ID
- P54855
- Uniprot Name
- UDP-glucuronosyltransferase 2B15
- Molecular Weight
- 61035.815 Da
References
- Ghosal A, Hapangama N, Yuan Y, Achanfuo-Yeboah J, Iannucci R, Chowdhury S, Alton K, Patrick JE, Zbaida S: Identification of human UDP-glucuronosyltransferase enzyme(s) responsible for the glucuronidation of ezetimibe (Zetia). Drug Metab Dispos. 2004 Mar;32(3):314-20. [Article]
- Kosoglou T, Statkevich P, Johnson-Levonas AO, Paolini JF, Bergman AJ, Alton KB: Ezetimibe: a review of its metabolism, pharmacokinetics and drug interactions. Clin Pharmacokinet. 2005;44(5):467-94. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:10702251, PubMed:15470161, PubMed:15472229, PubMed:17442341, PubMed:18674515, PubMed:18719240, PubMed:19022937, PubMed:23288867, PubMed:23756265, PubMed:26220143). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:15470161, PubMed:18674515, PubMed:23756265). Catalyzes the glucuronidation of endogenous steroid hormones such as androgens (epitestosterone, androsterone) and estrogens (estradiol, epiestradiol, estriol, catechol estrogens) (PubMed:15472229, PubMed:17442341, PubMed:18719240, PubMed:19022937, PubMed:2159463, PubMed:23288867, PubMed:26220143). Also regulates the levels of retinoic acid, a major metabolite of vitamin A involved in apoptosis, cellular growth and differentiation, and embryonic development (PubMed:10702251). Contributes to bile acid (BA) detoxification by catalyzing the glucuronidation of BA substrates, which are natural detergents for dietary lipids absorption (PubMed:23756265). Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonist losartan, caderastan and zolarsatan, drugs which can inhibit the effect of angiotensin II (PubMed:18674515). Also metabolizes mycophenolate, an immunosuppressive agent (PubMed:15470161)
- Specific Function
- glucuronosyltransferase activity
- Gene Name
- UGT2B7
- Uniprot ID
- P16662
- Uniprot Name
- UDP-glucuronosyltransferase 2B7
- Molecular Weight
- 60720.15 Da
References
- Ghosal A, Hapangama N, Yuan Y, Achanfuo-Yeboah J, Iannucci R, Chowdhury S, Alton K, Patrick JE, Zbaida S: Identification of human UDP-glucuronosyltransferase enzyme(s) responsible for the glucuronidation of ezetimibe (Zetia). Drug Metab Dispos. 2004 Mar;32(3):314-20. [Article]
- Kosoglou T, Statkevich P, Johnson-Levonas AO, Paolini JF, Bergman AJ, Alton KB: Ezetimibe: a review of its metabolism, pharmacokinetics and drug interactions. Clin Pharmacokinet. 2005;44(5):467-94. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- In vitro of human liver microsomes, the IC50 value was 7 μmol/L. In vivo follow-up studies suggest no clinically significant potential for interaction.
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Kosoglou T, Statkevich P, Johnson-Levonas AO, Paolini JF, Bergman AJ, Alton KB: Ezetimibe: a review of its metabolism, pharmacokinetics and drug interactions. Clin Pharmacokinet. 2005;44(5):467-94. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- According to an in vitro assay, the IC50 value was 31 μmol/L in human liver microsomes. The FDA label indicates that this drug is unlikely to interact with CYP2C8 substrates.
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Primarily catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) with a preference for the last double bond (PubMed:15766564, PubMed:19965576, PubMed:7574697). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes all trans-retinoic acid toward its 4-hydroxylated form (PubMed:11093772). Displays 16-alpha hydroxylase activity toward estrogen steroid hormones, 17beta-estradiol (E2) and estrone (E1) (PubMed:14559847). Plays a role in the oxidative metabolism of xenobiotics. It is the principal enzyme responsible for the metabolism of the anti-cancer drug paclitaxel (taxol) (PubMed:26427316)
- Specific Function
- arachidonic acid epoxygenase activity
- Gene Name
- CYP2C8
- Uniprot ID
- P10632
- Uniprot Name
- Cytochrome P450 2C8
- Molecular Weight
- 55824.275 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:12181437, PubMed:15472229, PubMed:18004206, PubMed:18004212, PubMed:18719240, PubMed:19830808, PubMed:23288867). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:12181437, PubMed:18004206, PubMed:18004212). Catalyzes the glucuronidation of endogenous estrogen hormones such as estradiol, estrone and estriol (PubMed:15472229, PubMed:18719240, PubMed:23288867). Involved in the glucuronidation of bilirubin, a degradation product occurring in the normal catabolic pathway that breaks down heme in vertebrates (PubMed:17187418, PubMed:18004206, PubMed:19830808, PubMed:24525562). Also catalyzes the glucuronidation the isoflavones genistein, daidzein, glycitein, formononetin, biochanin A and prunetin, which are phytoestrogens with anticancer and cardiovascular properties (PubMed:18052087, PubMed:19545173). Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonist losartan, a drug which can inhibit the effect of angiotensin II (PubMed:18674515). Involved in the biotransformation of 7-ethyl-10-hydroxycamptothecin (SN-38), the pharmacologically active metabolite of the anticancer drug irinotecan (PubMed:12181437, PubMed:18004212, PubMed:20610558)
- Specific Function
- enzyme binding
- Gene Name
- UGT1A1
- Uniprot ID
- P22309
- Uniprot Name
- UDP-glucuronosyltransferase 1A1
- Molecular Weight
- 59590.91 Da
References
- Oswald S, Nassif A, Modess C, Keiser M, Ulrich A, Runge D, Hanke U, Lutjohann D, Engel A, Weitschies W, Siegmund W: Drug interactions between the immunosuppressant tacrolimus and the cholesterol absorption inhibitor ezetimibe in healthy volunteers. Clin Pharmacol Ther. 2011 Apr;89(4):524-8. doi: 10.1038/clpt.2011.4. Epub 2011 Mar 2. [Article]
- Kosoglou T, Statkevich P, Johnson-Levonas AO, Paolini JF, Bergman AJ, Alton KB: Ezetimibe: a review of its metabolism, pharmacokinetics and drug interactions. Clin Pharmacokinet. 2005;44(5):467-94. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- ATP-dependent translocase ABCB1
- Molecular Weight
- 141477.255 Da
References
- Oswald S, Nassif A, Modess C, Keiser M, Ulrich A, Runge D, Hanke U, Lutjohann D, Engel A, Weitschies W, Siegmund W: Drug interactions between the immunosuppressant tacrolimus and the cholesterol absorption inhibitor ezetimibe in healthy volunteers. Clin Pharmacol Ther. 2011 Apr;89(4):524-8. doi: 10.1038/clpt.2011.4. Epub 2011 Mar 2. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- ATP-dependent transporter of the ATP-binding cassette (ABC) family that binds and hydrolyzes ATP to enable active transport of various substrates including many drugs, toxicants and endogenous compound across cell membranes. Transports a wide variety of conjugated organic anions such as sulfate-, glucuronide- and glutathione (GSH)-conjugates of endo- and xenobiotics substrates (PubMed:10220572, PubMed:10421658, PubMed:11500505, PubMed:16332456). Mediates hepatobiliary excretion of mono- and bis-glucuronidated bilirubin molecules and therefore play an important role in bilirubin detoxification (PubMed:10421658). Mediates also hepatobiliary excretion of others glucuronide conjugates such as 17beta-estradiol 17-glucosiduronic acid and leukotriene C4 (PubMed:11500505). Transports sulfated bile salt such as taurolithocholate sulfate (PubMed:16332456). Transports various anticancer drugs, such as anthracycline, vinca alkaloid and methotrexate and HIV-drugs such as protease inhibitors (PubMed:10220572, PubMed:11500505, PubMed:12441801). Confers resistance to several anti-cancer drugs including cisplatin, doxorubicin, epirubicin, methotrexate, etoposide and vincristine (PubMed:10220572, PubMed:11500505)
- Specific Function
- ABC-type glutathione S-conjugate transporter activity
- Gene Name
- ABCC2
- Uniprot ID
- Q92887
- Uniprot Name
- ATP-binding cassette sub-family C member 2
- Molecular Weight
- 174205.64 Da
References
- Oswald S, Nassif A, Modess C, Keiser M, Ulrich A, Runge D, Hanke U, Lutjohann D, Engel A, Weitschies W, Siegmund W: Drug interactions between the immunosuppressant tacrolimus and the cholesterol absorption inhibitor ezetimibe in healthy volunteers. Clin Pharmacol Ther. 2011 Apr;89(4):524-8. doi: 10.1038/clpt.2011.4. Epub 2011 Mar 2. [Article]
- de Waart DR, Vlaming ML, Kunne C, Schinkel AH, Oude Elferink RP: Complex pharmacokinetic behavior of ezetimibe depends on abcc2, abcc3, and abcg2. Drug Metab Dispos. 2009 Aug;37(8):1698-702. doi: 10.1124/dmd.108.026146. Epub 2009 May 14. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- ATP-dependent transporter of the ATP-binding cassette (ABC) family that binds and hydrolyzes ATP to enable active transport of various substrates including many drugs, toxicants and endogenous compound across cell membranes (PubMed:10359813, PubMed:11581266, PubMed:15083066). Transports glucuronide conjugates such as bilirubin diglucuronide, estradiol-17-beta-o-glucuronide and GSH conjugates such as leukotriene C4 (LTC4) (PubMed:11581266, PubMed:15083066). Transports also various bile salts (taurocholate, glycocholate, taurochenodeoxycholate-3-sulfate, taurolithocholate- 3-sulfate) (By similarity). Does not contribute substantially to bile salt physiology but provides an alternative route for the export of bile acids and glucuronides from cholestatic hepatocytes (By similarity). May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can confer resistance to various anticancer drugs, methotrexate, tenoposide and etoposide, by decreasing accumulation of these drugs in cells (PubMed:10359813, PubMed:11581266)
- Specific Function
- ABC-type bile acid transporter activity
- Gene Name
- ABCC3
- Uniprot ID
- O15438
- Uniprot Name
- ATP-binding cassette sub-family C member 3
- Molecular Weight
- 169341.14 Da
References
- de Waart DR, Vlaming ML, Kunne C, Schinkel AH, Oude Elferink RP: Complex pharmacokinetic behavior of ezetimibe depends on abcc2, abcc3, and abcg2. Drug Metab Dispos. 2009 Aug;37(8):1698-702. doi: 10.1124/dmd.108.026146. Epub 2009 May 14. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Mediates the Na(+)-independent uptake of organic anions (PubMed:10358072, PubMed:15159445, PubMed:17412826). Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (dehydroepiandrosterone 3-sulfate, 17-beta-glucuronosyl estradiol, and estrone 3-sulfate), as well as eicosanoids (prostaglandin E2, thromboxane B2, leukotriene C4, and leukotriene E4), and thyroid hormones (T4/L-thyroxine, and T3/3,3',5'-triiodo-L-thyronine) (PubMed:10358072, PubMed:10601278, PubMed:10873595, PubMed:11159893, PubMed:12196548, PubMed:12568656, PubMed:15159445, PubMed:15970799, PubMed:16627748, PubMed:17412826, PubMed:19129463, PubMed:26979622). Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop (PubMed:22232210). Involved in the clearance of endogenous and exogenous substrates from the liver (PubMed:10358072, PubMed:10601278). Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition (PubMed:26383540). May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins), such as pravastatin and pitavastatin, a clinically important class of hypolipidemic drugs (PubMed:10601278, PubMed:15159445, PubMed:15970799). May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drug methotrexate (PubMed:23243220). May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver (PubMed:16624871, PubMed:16627748). Shows a pH-sensitive substrate specificity towards prostaglandin E2 and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment (PubMed:19129463). Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions (PubMed:19129463)
- Specific Function
- bile acid transmembrane transporter activity
- Gene Name
- SLCO1B1
- Uniprot ID
- Q9Y6L6
- Uniprot Name
- Solute carrier organic anion transporter family member 1B1
- Molecular Weight
- 76447.99 Da
References
- Oswald S, Nassif A, Modess C, Keiser M, Ulrich A, Runge D, Hanke U, Lutjohann D, Engel A, Weitschies W, Siegmund W: Drug interactions between the immunosuppressant tacrolimus and the cholesterol absorption inhibitor ezetimibe in healthy volunteers. Clin Pharmacol Ther. 2011 Apr;89(4):524-8. doi: 10.1038/clpt.2011.4. Epub 2011 Mar 2. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Broad substrate specificity ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes a wide variety of physiological compounds, dietary toxins and xenobiotics from cells (PubMed:11306452, PubMed:12958161, PubMed:19506252, PubMed:20705604, PubMed:28554189, PubMed:30405239, PubMed:31003562). Involved in porphyrin homeostasis, mediating the export of protoporphyrin IX (PPIX) from both mitochondria to cytosol and cytosol to extracellular space, it also functions in the cellular export of heme (PubMed:20705604, PubMed:23189181). Also mediates the efflux of sphingosine-1-P from cells (PubMed:20110355). Acts as a urate exporter functioning in both renal and extrarenal urate excretion (PubMed:19506252, PubMed:20368174, PubMed:22132962, PubMed:31003562, PubMed:36749388). In kidney, it also functions as a physiological exporter of the uremic toxin indoxyl sulfate (By similarity). Also involved in the excretion of steroids like estrone 3-sulfate/E1S, 3beta-sulfooxy-androst-5-en-17-one/DHEAS, and other sulfate conjugates (PubMed:12682043, PubMed:28554189, PubMed:30405239). Mediates the secretion of the riboflavin and biotin vitamins into milk (By similarity). Extrudes pheophorbide a, a phototoxic porphyrin catabolite of chlorophyll, reducing its bioavailability (By similarity). Plays an important role in the exclusion of xenobiotics from the brain (Probable). It confers to cells a resistance to multiple drugs and other xenobiotics including mitoxantrone, pheophorbide, camptothecin, methotrexate, azidothymidine, and the anthracyclines daunorubicin and doxorubicin, through the control of their efflux (PubMed:11306452, PubMed:12477054, PubMed:15670731, PubMed:18056989, PubMed:31254042). In placenta, it limits the penetration of drugs from the maternal plasma into the fetus (By similarity). May play a role in early stem cell self-renewal by blocking differentiation (By similarity)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCG2
- Uniprot ID
- Q9UNQ0
- Uniprot Name
- Broad substrate specificity ATP-binding cassette transporter ABCG2
- Molecular Weight
- 72313.47 Da
References
- de Waart DR, Vlaming ML, Kunne C, Schinkel AH, Oude Elferink RP: Complex pharmacokinetic behavior of ezetimibe depends on abcc2, abcc3, and abcg2. Drug Metab Dispos. 2009 Aug;37(8):1698-702. doi: 10.1124/dmd.108.026146. Epub 2009 May 14. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Catalyzes the transport of the major hydrophobic bile salts, such as taurine and glycine-conjugated cholic acid across the canalicular membrane of hepatocytes in an ATP-dependent manner, therefore participates in hepatic bile acid homeostasis and consequently to lipid homeostasis through regulation of biliary lipid secretion in a bile salts dependent manner (PubMed:15791618, PubMed:16332456, PubMed:18985798, PubMed:19228692, PubMed:20010382, PubMed:20398791, PubMed:22262466, PubMed:24711118, PubMed:29507376, PubMed:32203132). Transports taurine-conjugated bile salts more rapidly than glycine-conjugated bile salts (PubMed:16332456). Also transports non-bile acid compounds, such as pravastatin and fexofenadine in an ATP-dependent manner and may be involved in their biliary excretion (PubMed:15901796, PubMed:18245269)
- Specific Function
- ABC-type bile acid transporter activity
- Gene Name
- ABCB11
- Uniprot ID
- O95342
- Uniprot Name
- Bile salt export pump
- Molecular Weight
- 146405.83 Da
References
- Pedersen JM, Matsson P, Bergstrom CA, Hoogstraate J, Noren A, LeCluyse EL, Artursson P: Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43. doi: 10.1093/toxsci/kft197. Epub 2013 Sep 6. [Article]
Drug created at June 13, 2005 13:24 / Updated at October 29, 2024 14:47