Explore a selection of our essential drug information below, or:
Identification
- Summary
Gemfibrozil is a lipid regulator that is used in the reduction of serum triglyceride levels in high-risk patients with hyperlipidemia.
- Brand Names
- Lopid
- Generic Name
- Gemfibrozil
- DrugBank Accession Number
- DB01241
- Background
Gemfibrozil is a fibric acid agent, similar to clofibrate, used to treat Type IIb, IV, and V hyperlipidemias.3,11 Gemfibrozil is not a first line treatment and is prescribed to patients who have not responded adequately to weight loss, diet, exercise, and other medications.11
Gemfibrozil was granted FDA approval on 21 December 1981.11
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Gemfibrozil (DB01241)
- Weight
- Average: 250.3334
Monoisotopic: 250.15689457 - Chemical Formula
- C15H22O3
- Synonyms
- 2,2-Dimethyl-5-(2,5-dimethylphenoxy)valeriansäure
- 2,2-Dimethyl-5-(2,5-xylyloxy)valeriansäure
- 2,2-Dimethyl-5-(2,5-xylyloxy)valeric acid
- Gemfibrozil
- Gemfibrozilo
- Gemfibrozilum
- External IDs
- CI-719
Pharmacology
- Indication
Gemfibrozil is indicated to treat patients with Types IV and V hyperlipidemia who have elevated serum triglycerides (usually above 2000mg/dL), elevated VLDL cholesterol, fasting chylomicrons, are at risk of developing pancreatitis, and do not adequately respond to dietary restrictions.11 Gemfibrozil is also indicated to reduce the risk of developing coronary heart disease in patients with Type IIb hyperlipidemia without history or symptoms of coronary heart disease; who do not adequately respond to weight loss, diet, exercise, and other medications; and have low HDL, raised LDL, and raised triglycerides.11
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 Prevention of Coronary heart disease •••••••••••• Management of Frederickson type iv hypertriglyceridemia •••••••••••• Management of Frederickson type v hypertriglyceridemia •••••••••••• - 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
Gemfibrozil alters lipid metabolism to treat patients with hyperlipidemia.11 The duration of action requires twice daily dosing as the mean residence time of gemfibrozil is up to 9.6h in patients with chronic renal failure.7 Gemfibrozil has a wide therapeutic index as trials with twice the standard dose were not associated with severe side effects.8,11 Patients taking gemfibrozil may be at an increased risk of developing cholelithiasis and cholecystitis, as seen in patients taking clofibrate.11
- Mechanism of action
Gemfibrozil activates peroxisome proliferator-activated receptor-α (PPARα), which alters lipid metabolism.3 This activation leads to increased HDL, apo AI, apo AII, lipoprotein lipase (LPL), inhibition of apo B synthesis, peripheral lipolysis, decreased removal of free fatty acids by the liver, and increased clearance of apoB.1,3,11
Upregulated LPL reduces plasma triglyceride levels.1,3,11 Decreased hepatic removal of fatty acids decreases the production of triglycerides.1,3,11 The effects on apoB synthesis and clearance decrease VLDL production which also reduce plasma triglyceride levels.1,3,11
Gemfibrozil's glucuronide metabolite is also an inhibitor of CYP2C8.4
Target Actions Organism APeroxisome proliferator-activated receptor alpha agonistHumans ALipoprotein lipase activatorHumans USolute carrier organic anion transporter family member 1B1 inhibitorHumans UOrganic anion transporter 3 inhibitorHumans USolute carrier organic anion transporter family member 2B1 inhibitorHumans USolute carrier organic anion transporter family member 1B3 inhibitorHumans - Absorption
Gemfibrozil is absorbed from the gastrointestinal tract.11
In healthy volunteers, a 900mg oral dose of gemfibrozil has a Cmax of 46±16µg/mL with a Tmax of 2.2±1.1h.7 In patients with chronic renal failure, gemfibrozil has a Cmax of 13.8±11.1µg/mL with a Tmax of 2.3±1.0h.7 In patients with liver disease, gemfibrozil has a Cmax of 23.0±10.3µg/mL with a Tmax of 2.6±1.7h.7
- Volume of distribution
The volume of distribution of gemfibrozil is estimated to be 0.8L/kg.10
- Protein binding
Gemfibrozil is 99% protein bound.3,6 It is 98.6% bound to serum albumin, 0.8% bound to erythrocytes, and 0.8% unbound.5,6 There is negligible binding to alpha-1-acid glycoprotein.6
- Metabolism
Gemfibrozil undergoes hydroxylation at the 5'-methyl and 4' positions to form the M1 and M2 metaolites respectively9. Gemfibrozil also undergoes O-glucuronidation to form gemfibrozil 1-beta glucuronide, an inhibitor of CYP2C8.4 This O-glucuronidation is primarily mediated by UGT2B7, but also by UGT1A1, UGT1A3, UGT1A9, UGT2B4, UGT2B17.4
Hover over products below to view reaction partners
- Route of elimination
Approximately 70% of a dose of gemfibrozil is eliminated in the urine.11 The majority of a dose is eliminated as a glucuronide conjugate and <2% is elimiinated as the unmetabolized drug.11 6% of a dose is eliminated in the feces.11
In healthy volunteers, 0.02-0.15% of a dose was detected in the urine as unmetabolized gemfibrozil, with 7-14% detected as conjugated metabolites.7 In patients with renal failure, trace amounts of unmetabolized gemfibrozil is present in the urine, with 0.5-9.8% detected as conjugated metabolites.7 In patients with liver disease, 0.1-0.2% of a dose was detected in the urine as unmetabolized gemfibrozil, with 25-50% detected as conjugated metabolites.7
- Half-life
Gemfibrozil has a plasma half-life of 1.5 hours.11 In patients with renal failure the half life is 2.4h and in patients with liver disease the half life is 2.1h.7
- Clearance
The clearance of gemfibrozil is estimated to be 6.0L/h.10
- 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
The oral TDLO of gemfibrozil in humans is 18gm/kg/3Y.12 The oral LD50 in mice is 2218mg/kg and in rats is 1414mg/kg.12 The intraperitoneal LD50 in rats is 445mg/kg.12
Patients experiencing an overdose may present with abdominal cramps, adnormal liver function tests, diarrhea, increased CPK, joint and muscle pain, nausea, and vomiting.11 Patients should be treated with symptomatic and supportive measures.11
- 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 softwareAbacavir The metabolism of Abacavir can be decreased when combined with Gemfibrozil. Abametapir The serum concentration of Gemfibrozil can be increased when it is combined with Abametapir. Abrocitinib The metabolism of Abrocitinib can be decreased when combined with Gemfibrozil. Aceclofenac Aceclofenac may decrease the excretion rate of Gemfibrozil which could result in a higher serum level. Acemetacin Acemetacin may decrease the excretion rate of Gemfibrozil which could result in a higher serum level. - Food Interactions
- Take before a meal. Take 30 minutes before meals.
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
- Gemlipid (Farmellas Enterprises) / Gen-Fibro / Genlip (Teofarma) / Jezil / Lipur (Pfizer)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Gemfibrozil Tablet 600 mg/1 Oral Watson Pharmaceuticals 2007-01-01 Not applicable US 
Gemfibrozil Cap 300mg Capsule 300 mg / cap Oral Omni Laboratories Division, Warner Lambert Canada Inc. 1990-12-31 2003-07-04 Canada 
Gemfibrozil Tab 600mg Tablet 600 mg Oral Omni Laboratories Division, Warner Lambert Canada Inc. 1991-12-31 2003-07-04 Canada Gemfibrozil-300 - Cap Capsule 300 mg Oral Pro Doc Limitee 1995-12-31 2010-07-13 Canada Gemfibrozil-600 - Tab 600mg Tablet 600 mg Oral Pro Doc Limitee 1995-12-31 2015-07-10 Canada - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Apo-gemfibrozil Tablet 600 mg Oral Apotex Corporation 1993-12-31 Not applicable Canada Apo-gemfibrozil Cap 300mg USP Capsule 300 mg Oral Apotex Corporation 1993-12-31 Not applicable Canada Dom-gemfibrozil Capsule 300 mg Oral Dominion Pharmacal 2000-03-10 Not applicable Canada Dom-gemfibrozil Tablet 600 mg Oral Dominion Pharmacal 1998-10-22 2013-04-05 Canada Gemfibrozil Tablet 600 mg/1 Oral Viona Pharmaceuticals Inc 2020-02-21 Not applicable US
Categories
- ATC Codes
- C10AB04 — Gemfibrozil
- Drug Categories
- Acids, Acyclic
- Agents Causing Muscle Toxicity
- Benzene Derivatives
- Butyrates
- Chemically-Induced Disorders
- Cytochrome P-450 CYP1A2 Inhibitors
- Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2C19 Inhibitors
- Cytochrome P-450 CYP2C19 Inhibitors (strong)
- Cytochrome P-450 CYP2C8 Inducers
- Cytochrome P-450 CYP2C8 Inducers (strength unknown)
- Cytochrome P-450 CYP2C8 Inhibitors
- Cytochrome P-450 CYP2C8 Inhibitors (strong)
- Cytochrome P-450 CYP2C9 Inhibitors
- Cytochrome P-450 CYP2C9 Inhibitors (strong)
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Enzyme Inducers
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Drugs causing inadvertant photosensitivity
- Drugs that are Mainly Renally Excreted
- Enzyme Inhibitors
- Ethers
- Fatty Acids
- Fatty Acids, Volatile
- Fibric Acid Derivatives
- Fibric Acids
- Hypolipidemic Agents
- Hypolipidemic Agents Indicated for Hyperlipidemia
- Isobutyrates
- Lipid Modifying Agents
- Lipid Modifying Agents, Plain
- Lipid Regulating Agents
- Lipids
- Non-statin Hypolipidemic Agents Indicated for Hyperlipidemia
- Noxae
- OAT3/SLC22A8 Inhibitors
- OATP1B1/SLCO1B1 Inhibitors
- OATP1B3 inhibitors
- Organic Anion Transporting Polypeptide 2B1 Inhibitors
- Pentanoic Acids
- Peroxisome Proliferator Receptor alpha Agonist
- Peroxisome Proliferator-activated Receptor alpha Agonists
- Phenols
- Phenyl Ethers
- Photosensitizing Agents
- Toxic Actions
- UGT1A1 Inhibitors
- UGT1A1 Substrates
- UGT1A3 Inhibitors
- UGT1A3 substrates
- UGT1A9 Substrates
- UGT2B17 substrates
- UGT2B7 substrates
- Valerates
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as phenol ethers. These are aromatic compounds containing an ether group substituted with a benzene ring.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Phenol ethers
- Sub Class
- Not Available
- Direct Parent
- Phenol ethers
- Alternative Parents
- p-Xylenes / Phenoxy compounds / Alkyl aryl ethers / Monocarboxylic acids and derivatives / Carboxylic acids / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
- Substituents
- Alkyl aryl ether / Aromatic homomonocyclic compound / Carbonyl group / Carboxylic acid / Carboxylic acid derivative / Ether / Hydrocarbon derivative / Monocarboxylic acid or derivatives / Monocyclic benzene moiety / Organic oxide
- Molecular Framework
- Aromatic homomonocyclic compounds
- External Descriptors
- aromatic ether (CHEBI:5296)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- Q8X02027X3
- CAS number
- 25812-30-0
- InChI Key
- HEMJJKBWTPKOJG-UHFFFAOYSA-N
- InChI
- InChI=1S/C15H22O3/c1-11-6-7-12(2)13(10-11)18-9-5-8-15(3,4)14(16)17/h6-7,10H,5,8-9H2,1-4H3,(H,16,17)
- IUPAC Name
- 5-(2,5-dimethylphenoxy)-2,2-dimethylpentanoic acid
- SMILES
- CC1=CC(OCCCC(C)(C)C(O)=O)=C(C)C=C1
References
- Synthesis Reference
Gianfranco Piccoli, Antonio Tarquini, Giovanni Frare, "Process for the preparation of gemfibrozil." U.S. Patent US5654476, issued May, 1980.
US5654476- General References
- Saku K, Gartside PS, Hynd BA, Kashyap ML: Mechanism of action of gemfibrozil on lipoprotein metabolism. J Clin Invest. 1985 May;75(5):1702-12. doi: 10.1172/JCI111879. [Article]
- Okerholm RA, Keeley FJ, Peterson FE, Glazko AJ: The metabolism of gemfibrozil. Proc R Soc Med. 1976;69 Suppl 2:11-4. [Article]
- Quintanilla Rodriguez BS, Correa R: Gemfibrozil . [Article]
- Mano Y, Usui T, Kamimura H: The UDP-glucuronosyltransferase 2B7 isozyme is responsible for gemfibrozil glucuronidation in the human liver. Drug Metab Dispos. 2007 Nov;35(11):2040-4. doi: 10.1124/dmd.107.017269. Epub 2007 Aug 1. [Article]
- Sallustio BC, Fairchild BA, Pannall PR: Interaction of human serum albumin with the electrophilic metabolite 1-O-gemfibrozil-beta-D-glucuronide. Drug Metab Dispos. 1997 Jan;25(1):55-60. [Article]
- Hamberger C, Barre J, Zini R, Taiclet A, Houin G, Tillement JP: In vitro binding study of gemfibrozil to human serum proteins and erythrocytes: interactions with other drugs. Int J Clin Pharmacol Res. 1986;6(6):441-9. [Article]
- Knauf H, Kolle EU, Mutschler E: Gemfibrozil absorption and elimination in kidney and liver disease. Klin Wochenschr. 1990 Jul 5;68(13):692-8. doi: 10.1007/bf01667018. [Article]
- Fereshetian AG, Davidson M, Haber H, Black DM: Gemfibrozil treatment in patients with elevated lipoprotein a: a pilot study. Clin Drug Investig. 1998;16(1):1-7. doi: 10.2165/00044011-199816010-00001. [Article]
- Takahiro M, Haruo I, Toshihiko, I: Identification of Gemfibrozil Metabolites, Produced as Positional Isomers in Human Liver Microsomes, by On-line Analyses Using Liquid Chromatography/Mass Spectrometry and Liquid Chromatography/Nuclear Magnetic Resonance Spectroscopy J. Mass Spectrom. Soc. Jpn.. 2004 Jun 6;52(5):277-283. [Article]
- Varma MV, Lin J, Bi YA, Kimoto E, Rodrigues AD: Quantitative Rationalization of Gemfibrozil Drug Interactions: Consideration of Transporters-Enzyme Interplay and the Role of Circulating Metabolite Gemfibrozil 1-O-beta-Glucuronide. Drug Metab Dispos. 2015 Jul;43(7):1108-18. doi: 10.1124/dmd.115.064303. Epub 2015 May 4. [Article]
- FDA Approved Drug Products: Gemfibrozil Oral Tablets [Link]
- Cayman Chemicals: Gemfibrozil MSDS [Link]
- External Links
- Human Metabolome Database
- HMDB0015371
- KEGG Drug
- D00334
- KEGG Compound
- C07020
- PubChem Compound
- 3463
- PubChem Substance
- 46508264
- ChemSpider
- 3345
- BindingDB
- 50110590
- 4719
- ChEBI
- 5296
- ChEMBL
- CHEMBL457
- ZINC
- ZINC000001530641
- Therapeutic Targets Database
- DAP000210
- PharmGKB
- PA449750
- Guide to Pharmacology
- GtP Drug Page
- PDBe Ligand
- 4TX
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- PDRhealth
- PDRhealth Drug Page
- Wikipedia
- Gemfibrozil
- PDB Entries
- 5boj / 7qfe
- FDA label
- Download (260 KB)
- MSDS
- Download (74.3 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 Completed Not Available Healthy Volunteers (HV) 1 somestatus stop reason just information to hide 4 Completed Treatment Healthy Volunteers (HV) 1 somestatus stop reason just information to hide 4 Withdrawn Treatment Atherosclerosis 1 somestatus stop reason just information to hide 3 Completed Treatment Coronary Heart Disease (CHD) 1 somestatus stop reason just information to hide 3 Not Yet Recruiting Treatment Juvenile Neuronal Ceroid Lipofuscinosis (CLN3, Batten Disease) 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Ancheng Pharma Limited
- Apotex Inc.
- Blu Pharmaceuticals LLC
- Bryant Ranch Prepack
- Camber Pharmaceuticals Inc.
- Caraco Pharmaceutical Labs
- Cardinal Health
- Corepharma LLC
- Coupler Enterprises Inc.
- DAVA Pharmaceuticals
- Dept Health Central Pharmacy
- DHHS Program Support Center Supply Service Center
- Direct Dispensing Inc.
- Dispensing Solutions
- Global Pharmaceuticals
- Golden State Medical Supply Inc.
- Heartland Repack Services LLC
- InvaGen Pharmaceuticals Inc.
- Kaiser Foundation Hospital
- Liberty Pharmaceuticals
- Major Pharmaceuticals
- Murfreesboro Pharmaceutical Nursing Supply
- Norwich Pharmaceuticals Inc.
- Novopharm Ltd.
- Nucare Pharmaceuticals Inc.
- Palmetto Pharmaceuticals Inc.
- Patheon Inc.
- PD-Rx Pharmaceuticals Inc.
- Pfizer Inc.
- Physicians Total Care Inc.
- Preferred Pharmaceuticals Inc.
- Prepackage Specialists
- Prepak Systems Inc.
- Professional Co.
- Rebel Distributors Corp.
- Remedy Repack
- Sandhills Packaging Inc.
- Southwood Pharmaceuticals
- Sun Pharmaceutical Industries Ltd.
- Teva Pharmaceutical Industries Ltd.
- Torpharm Inc.
- Tya Pharmaceuticals
- UDL Laboratories
- Va Cmop Dallas
- Vangard Labs Inc.
- Watson Pharmaceuticals
- West-Ward Pharmaceuticals
- Zydus Pharmaceuticals
- Dosage Forms
Form Route Strength Tablet Oral 300 mg Tablet Oral Granule 1200 MG Tablet Oral 600 mg/1 Tablet Oral 900 MG Tablet, coated Oral 600 mg/1 Tablet, film coated Oral 600 mg/1 Capsule Oral 300 mg / cap Tablet, coated Oral 60000000 mg Tablet, film coated Oral 900 mg Tablet, delayed release Oral 600 mg Tablet, coated Oral Capsule Oral 600 mg Capsule, coated Oral 300 mg Granule, for suspension Oral 1200 mg Granule, for suspension Oral 900 mg Tablet, film coated Oral Capsule Oral Granule Granule, for suspension Oral Granule 900 MG Tablet Oral 900.000 mg Tablet Oral 600 mg / tab Tablet Oral 600.00 mg Capsule Oral 300 mg Tablet, coated Oral 900 mg Tablet, coated Oral 600 mg Tablet, film coated Oral 600 mg Tablet Oral 600 mg - Prices
Unit description Cost Unit Gemfibrozil powder 2.88USD g Lopid 600 mg tablet 2.07USD tablet Gemfibrozil 600 mg tablet 1.8USD tablet Apo-Gemfibrozil 600 mg Tablet 0.65USD tablet Mylan-Gemfibrozil 600 mg Tablet 0.65USD tablet Novo-Gemfibrozil 600 mg Tablet 0.65USD tablet Nu-Gemfibrozil 600 mg Tablet 0.65USD tablet Pms-Gemfibrozil 600 mg Tablet 0.65USD tablet Lopid 300 mg Capsule 0.58USD capsule Apo-Gemfibrozil 300 mg Capsule 0.31USD capsule Mylan-Gemfibrozil 300 mg Capsule 0.31USD capsule Novo-Gemfibrozil 300 mg Capsule 0.31USD capsule Nu-Gemfibrozil 300 mg Capsule 0.31USD capsule Pms-Gemfibrozil 300 mg Capsule 0.31USD capsule DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 58-61 FDA Label boiling point (°C) 158.5 °C at 2.00E-02 mm Hg PhysProp logP 4.387 ChemSpider - Predicted Properties
Property Value Source Water Solubility 0.0278 mg/mL ALOGPS logP 3.61 ALOGPS logP 4.39 Chemaxon logS -4 ALOGPS pKa (Strongest Acidic) 4.42 Chemaxon pKa (Strongest Basic) -4.8 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 46.53 Å2 Chemaxon Rotatable Bond Count 6 Chemaxon Refractivity 71.82 m3·mol-1 Chemaxon Polarizability 28.9 Å3 Chemaxon Number of Rings 1 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.977 Blood Brain Barrier + 0.9213 Caco-2 permeable + 0.7918 P-glycoprotein substrate Substrate 0.5597 P-glycoprotein inhibitor I Non-inhibitor 0.8943 P-glycoprotein inhibitor II Non-inhibitor 0.8839 Renal organic cation transporter Non-inhibitor 0.8177 CYP450 2C9 substrate Non-substrate 0.7512 CYP450 2D6 substrate Non-substrate 0.9116 CYP450 3A4 substrate Substrate 0.6973 CYP450 1A2 substrate Inhibitor 0.9106 CYP450 2C9 inhibitor Inhibitor 0.8949 CYP450 2D6 inhibitor Non-inhibitor 0.9231 CYP450 2C19 inhibitor Non-inhibitor 0.9025 CYP450 3A4 inhibitor Non-inhibitor 0.8309 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8234 Ames test Non AMES toxic 0.7822 Carcinogenicity Non-carcinogens 0.8314 Biodegradation Not ready biodegradable 0.6759 Rat acute toxicity 2.2167 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9774 hERG inhibition (predictor II) Non-inhibitor 0.8701
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 168.9544048 predictedDarkChem Lite v0.1.0 [M-H]- 169.4125048 predictedDarkChem Lite v0.1.0 [M-H]- 168.9918048 predictedDarkChem Lite v0.1.0 [M-H]- 164.49422 predictedDeepCCS 1.0 (2019) [M+H]+ 169.3420048 predictedDarkChem Lite v0.1.0 [M+H]+ 169.1184048 predictedDarkChem Lite v0.1.0 [M+H]+ 169.5334048 predictedDarkChem Lite v0.1.0 [M+H]+ 166.85222 predictedDeepCCS 1.0 (2019) [M+Na]+ 169.3135048 predictedDarkChem Lite v0.1.0 [M+Na]+ 169.2560048 predictedDarkChem Lite v0.1.0 [M+Na]+ 169.0482048 predictedDarkChem Lite v0.1.0 [M+Na]+ 172.94537 predictedDeepCCS 1.0 (2019)
Targets
Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleylethanolamide, a naturally occurring lipid that regulates satiety. Receptor for peroxisome proliferators such as hypolipidemic drugs and fatty acids. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as a transcription activator for the ACOX1 and P450 genes. Transactivation activity requires heterodimerization with RXRA and is antagonized by NR2C2. May be required for the propagation of clock information to metabolic pathways regulated by PER2
- Specific Function
- DNA binding
- Gene Name
- PPARA
- Uniprot ID
- Q07869
- Uniprot Name
- Peroxisome proliferator-activated receptor alpha
- Molecular Weight
- 52224.595 Da
References
- Clavey V, Copin C, Mariotte MC, Bauge E, Chinetti G, Fruchart J, Fruchart JC, Dallongeville J, Staels B: Cell culture conditions determine apolipoprotein CIII secretion and regulation by fibrates in human hepatoma HepG2 cells. Cell Physiol Biochem. 1999;9(3):139-49. [Article]
- Bosse Y, Pascot A, Dumont M, Brochu M, Prud'homme D, Bergeron J, Despres JP, Vohl MC: Influences of the PPAR alpha-L162V polymorphism on plasma HDL(2)-cholesterol response of abdominally obese men treated with gemfibrozil. Genet Med. 2002 Jul-Aug;4(4):311-5. [Article]
- Pahan K, Jana M, Liu X, Taylor BS, Wood C, Fischer SM: Gemfibrozil, a lipid-lowering drug, inhibits the induction of nitric-oxide synthase in human astrocytes. J Biol Chem. 2002 Nov 29;277(48):45984-91. Epub 2002 Sep 18. [Article]
- Shoji Y, Sanekata A, Sato M, Imaizumi K: Preparation of antiserum against rat delta6-desaturase and its use to evaluate the desaturase protein levels in rats treated with gemfibrozil, a ligand for peroxisome proliferator-activated receptor alpha. Biosci Biotechnol Biochem. 2003 May;67(5):1177-8. [Article]
- Rizvi F, Iftikhar M, George JP: Beneficial effects of fish liver preparations of sea bass (Lates calcarifer) versus gemfibrozil in high fat diet-induced lipid-intolerant rats. J Med Food. 2003 Summer;6(2):123-8. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Activator
- General Function
- Key enzyme in triglyceride metabolism. Catalyzes the hydrolysis of triglycerides from circulating chylomicrons and very low density lipoproteins (VLDL), and thereby plays an important role in lipid clearance from the blood stream, lipid utilization and storage (PubMed:11342582, PubMed:27578112, PubMed:8675619). Although it has both phospholipase and triglyceride lipase activities it is primarily a triglyceride lipase with low but detectable phospholipase activity (PubMed:12032167, PubMed:7592706). Mediates margination of triglyceride-rich lipoprotein particles in capillaries (PubMed:24726386). Recruited to its site of action on the luminal surface of vascular endothelium by binding to GPIHBP1 and cell surface heparan sulfate proteoglycans (PubMed:11342582, PubMed:27811232)
- Specific Function
- 1-acyl-2-lysophosphatidylserine acylhydrolase activity
- Gene Name
- LPL
- Uniprot ID
- P06858
- Uniprot Name
- Lipoprotein lipase
- Molecular Weight
- 53162.07 Da
References
- 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
- Unknown
- Actions
- Inhibitor
- 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
- Sharma P, Holmes VE, Elsby R, Lambert C, Surry D: Validation of cell-based OATP1B1 assays to assess drug transport and the potential for drug-drug interaction to support regulatory submissions. Xenobiotica. 2010 Jan;40(1):24-37. doi: 10.3109/00498250903351013. [Article]
- Varma MV, Lin J, Bi YA, Kimoto E, Rodrigues AD: Quantitative Rationalization of Gemfibrozil Drug Interactions: Consideration of Transporters-Enzyme Interplay and the Role of Circulating Metabolite Gemfibrozil 1-O-beta-Glucuronide. Drug Metab Dispos. 2015 Jul;43(7):1108-18. doi: 10.1124/dmd.115.064303. Epub 2015 May 4. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Functions as an organic anion/dicarboxylate exchanger that couples organic anion uptake indirectly to the sodium gradient (PubMed:14586168, PubMed:15644426, PubMed:15846473, PubMed:16455804, PubMed:31553721). Transports organic anions such as estrone 3-sulfate (E1S) and urate in exchange for dicarboxylates such as glutarate or ketoglutarate (2-oxoglutarate) (PubMed:14586168, PubMed:15846473, PubMed:15864504, PubMed:22108572, PubMed:23832370). Plays an important role in the excretion of endogenous and exogenous organic anions, especially from the kidney and the brain (PubMed:11306713, PubMed:14586168, PubMed:15846473). E1S transport is pH- and chloride-dependent and may also involve E1S/cGMP exchange (PubMed:26377792). Responsible for the transport of prostaglandin E2 (PGE2) and prostaglandin F2(alpha) (PGF2(alpha)) in the basolateral side of the renal tubule (PubMed:11907186). Involved in the transport of neuroactive tryptophan metabolites kynurenate and xanthurenate (PubMed:22108572, PubMed:23832370). Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins (PubMed:28534121). May be involved in the basolateral transport of steviol, a metabolite of the popular sugar substitute stevioside (PubMed:15644426). May participate in the detoxification/ renal excretion of drugs and xenobiotics, such as the histamine H(2)-receptor antagonists fexofenadine and cimetidine, the antibiotic benzylpenicillin (PCG), the anionic herbicide 2,4-dichloro-phenoxyacetate (2,4-D), the diagnostic agent p-aminohippurate (PAH), the antiviral acyclovir (ACV), and the mycotoxin ochratoxin (OTA), by transporting these exogenous organic anions across the cell membrane in exchange for dicarboxylates such as 2-oxoglutarate (PubMed:11669456, PubMed:15846473, PubMed:16455804). Contributes to the renal uptake of potent uremic toxins (indoxyl sulfate (IS), indole acetate (IA), hippurate/N-benzoylglycine (HA) and 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF)), pravastatin, PCG, E1S and dehydroepiandrosterone sulfate (DHEAS), and is partly involved in the renal uptake of temocaprilat (an angiotensin-converting enzyme (ACE) inhibitor) (PubMed:14675047). May contribute to the release of cortisol in the adrenals (PubMed:15864504). Involved in one of the detoxification systems on the choroid plexus (CP), removes substrates such as E1S or taurocholate (TC), PCG, 2,4-D and PAH, from the cerebrospinal fluid (CSF) to the blood for eventual excretion in urine and bile (By similarity). Also contributes to the uptake of several other organic compounds such as the prostanoids prostaglandin E(2) and prostaglandin F(2-alpha), L-carnitine, and the therapeutic drugs allopurinol, 6-mercaptopurine (6-MP) and 5-fluorouracil (5-FU) (By similarity). Mediates the transport of PAH, PCG, and the statins pravastatin and pitavastatin, from the cerebrum into the blood circulation across the blood-brain barrier (BBB). In summary, plays a role in the efflux of drugs and xenobiotics, helping reduce their undesired toxicological effects on the body (By similarity)
- Specific Function
- organic anion transmembrane transporter activity
- Gene Name
- SLC22A8
- Uniprot ID
- Q8TCC7
- Uniprot Name
- Organic anion transporter 3
- Molecular Weight
- 59855.585 Da
References
- Varma MV, Lin J, Bi YA, Kimoto E, Rodrigues AD: Quantitative Rationalization of Gemfibrozil Drug Interactions: Consideration of Transporters-Enzyme Interplay and the Role of Circulating Metabolite Gemfibrozil 1-O-beta-Glucuronide. Drug Metab Dispos. 2015 Jul;43(7):1108-18. doi: 10.1124/dmd.115.064303. Epub 2015 May 4. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Mediates the Na(+)-independent transport of steroid sulfate conjugates and other specific organic anions (PubMed:10873595, PubMed:11159893, PubMed:11932330, PubMed:12724351, PubMed:14610227, PubMed:16908597, PubMed:18501590, PubMed:20507927, PubMed:22201122, PubMed:23531488, PubMed:25132355, PubMed:26383540, PubMed:27576593, PubMed:28408210, PubMed:29871943, PubMed:34628357). Responsible for the transport of estrone 3-sulfate (E1S) through the basal membrane of syncytiotrophoblast, highlighting a potential role in the placental absorption of fetal-derived sulfated steroids including the steroid hormone precursor dehydroepiandrosterone sulfate (DHEA-S) (PubMed:11932330, PubMed:12409283). Also facilitates the uptake of sulfated steroids at the basal/sinusoidal membrane of hepatocytes, therefore accounting for the major part of organic anions clearance of liver (PubMed:11159893). Mediates the intestinal uptake of sulfated steroids (PubMed:12724351, PubMed:28408210). Mediates the uptake of the neurosteroids DHEA-S and pregnenolone sulfate (PregS) into the endothelial cells of the blood-brain barrier as the first step to enter the brain (PubMed:16908597, PubMed:25132355). Also plays a role in the reuptake of neuropeptides such as substance P/TAC1 and vasoactive intestinal peptide/VIP released from retinal neurons (PubMed:25132355). May act as a heme transporter that promotes cellular iron availability via heme oxygenase/HMOX2 and independently of TFRC (PubMed:35714613). Also transports heme by-product coproporphyrin III (CPIII), and may be involved in their hepatic disposition (PubMed:26383540). Mediates the uptake of other substrates such as prostaglandins D2 (PGD2), E1 (PGE1) and E2 (PGE2), taurocholate, L-thyroxine, leukotriene C4 and thromboxane B2 (PubMed:10873595, PubMed:14610227, PubMed:19129463, PubMed:29871943, Ref.25). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable). Shows a pH-sensitive substrate specificity 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:14610227, PubMed:19129463, PubMed:22201122). The exact transport mechanism has not been yet deciphered but most likely involves an anion exchange, coupling the cellular uptake of organic substrate with the efflux of an anionic compound (PubMed:19129463, PubMed:20507927, PubMed:26277985). Hydrogencarbonate/HCO3(-) acts as a probable counteranion that exchanges for organic anions (PubMed:19129463). Cytoplasmic glutamate may also act as counteranion in the placenta (PubMed:26277985). An inwardly directed proton gradient has also been proposed as the driving force of E1S uptake with a (H(+):E1S) stoichiometry of (1:1) (PubMed:20507927)
- Specific Function
- bile acid transmembrane transporter activity
- Gene Name
- SLCO2B1
- Uniprot ID
- O94956
- Uniprot Name
- Solute carrier organic anion transporter family member 2B1
- Molecular Weight
- 76697.93 Da
References
- Noe J, Portmann R, Brun ME, Funk C: Substrate-dependent drug-drug interactions between gemfibrozil, fluvastatin and other organic anion-transporting peptide (OATP) substrates on OATP1B1, OATP2B1, and OATP1B3. Drug Metab Dispos. 2007 Aug;35(8):1308-14. doi: 10.1124/dmd.106.012930. Epub 2007 Apr 30. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Mediates the Na(+)-independent uptake of organic anions (PubMed:10779507, PubMed:15159445, PubMed:17412826). Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (17-beta-glucuronosyl estradiol, dehydroepiandrosterone sulfate (DHEAS), and estrone 3-sulfate), as well as eicosanoid leukotriene C4, prostaglandin E2 and L-thyroxine (T4) (PubMed:10779507, PubMed:11159893, PubMed:12568656, PubMed:15159445, PubMed:17412826, PubMed:19129463). Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions (PubMed:19129463). Shows a pH-sensitive substrate specificity towards sulfated steroids, taurocholate 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). Involved in the clearance of bile acids and organic anions from the liver (PubMed:22232210). Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop (PubMed:22232210). 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 pitavastatin, a clinically important class of hypolipidemic drugs (PubMed:15159445). May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drugs methotrexate and paclitaxel (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)
- Specific Function
- bile acid transmembrane transporter activity
- Gene Name
- SLCO1B3
- Uniprot ID
- Q9NPD5
- Uniprot Name
- Solute carrier organic anion transporter family member 1B3
- Molecular Weight
- 77402.175 Da
References
- Noe J, Portmann R, Brun ME, Funk C: Substrate-dependent drug-drug interactions between gemfibrozil, fluvastatin and other organic anion-transporting peptide (OATP) substrates on OATP1B1, OATP2B1, and OATP1B3. Drug Metab Dispos. 2007 Aug;35(8):1308-14. doi: 10.1124/dmd.106.012930. Epub 2007 Apr 30. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- 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
- Honkalammi J, Niemi M, Neuvonen PJ, Backman JT: Gemfibrozil is a strong inactivator of CYP2C8 in very small multiple doses. Clin Pharmacol Ther. 2012 May;91(5):846-55. doi: 10.1038/clpt.2011.313. [Article]
- Wang JS, Neuvonen M, Wen X, Backman JT, Neuvonen PJ: Gemfibrozil inhibits CYP2C8-mediated cerivastatin metabolism in human liver microsomes. Drug Metab Dispos. 2002 Dec;30(12):1352-6. [Article]
- Backman JT, Filppula AM, Niemi M, Neuvonen PJ: Role of Cytochrome P450 2C8 in Drug Metabolism and Interactions. Pharmacol Rev. 2016 Jan;68(1):168-241. doi: 10.1124/pr.115.011411. [Article]
- Flockhart Table of Drug Interactions [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of polyunsaturated fatty acids (PUFA) (PubMed:18577768, PubMed:19965576, PubMed:20972997). 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:18577768, PubMed:19965576, PubMed:20972997). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates PUFA specifically at the omega-1 position (PubMed:18577768). Catalyzes the epoxidation of double bonds of PUFA (PubMed:19965576, PubMed:20972997). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine. Hydroxylates fenbendazole at the 4' position (PubMed:23959307)
- Specific Function
- (R)-limonene 6-monooxygenase activity
- Gene Name
- CYP2C19
- Uniprot ID
- P33261
- Uniprot Name
- Cytochrome P450 2C19
- Molecular Weight
- 55944.565 Da
References
- Wen X, Wang JS, Backman JT, Kivisto KT, Neuvonen PJ: Gemfibrozil is a potent inhibitor of human cytochrome P450 2C9. Drug Metab Dispos. 2001 Nov;29(11):1359-61. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids and steroids (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). 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:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:15766564, PubMed:19965576, PubMed:7574697, PubMed:9866708). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Exhibits low catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes bisallylic hydroxylation and hydroxylation with double-bond migration of polyunsaturated fatty acids (PUFA) (PubMed:9435160, PubMed:9866708). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan (PubMed:25994031)
- Specific Function
- (R)-limonene 6-monooxygenase activity
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- Wen X, Wang JS, Backman JT, Kivisto KT, Neuvonen PJ: Gemfibrozil is a potent inhibitor of human cytochrome P450 2C9. Drug Metab Dispos. 2001 Nov;29(11):1359-61. [Article]
- Tornio A, Niemi M, Neuvonen PJ, Backman JT: Stereoselective interaction between the CYP2C8 inhibitor gemfibrozil and racemic ibuprofen. Eur J Clin Pharmacol. 2007 May;63(5):463-9. doi: 10.1007/s00228-007-0273-9. Epub 2007 Feb 27. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Data supported only by in vitro studies.
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). 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:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:11555828, PubMed:12865317). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2 (PubMed:11555828, PubMed:12865317). Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). May act as a major enzyme for all-trans retinoic acid biosynthesis in the liver. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376). Primarily catalyzes stereoselective epoxidation of the last double bond of polyunsaturated fatty acids (PUFA), displaying a strong preference for the (R,S) stereoisomer (PubMed:19965576). Catalyzes bisallylic hydroxylation and omega-1 hydroxylation of PUFA (PubMed:9435160). May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (PubMed:21068195). Plays a role in the oxidative metabolism of xenobiotics. Catalyzes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin (PubMed:14725854). Metabolizes caffeine via N3-demethylation (Probable)
- Specific Function
- aromatase activity
- Gene Name
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58406.915 Da
References
- Wen X, Wang JS, Backman JT, Kivisto KT, Neuvonen PJ: Gemfibrozil is a potent inhibitor of human cytochrome P450 2C9. Drug Metab Dispos. 2001 Nov;29(11):1359-61. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- 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
- Miller DB, Spence JD: Clinical pharmacokinetics of fibric acid derivatives (fibrates). Clin Pharmacokinet. 1998 Feb;34(2):155-62. doi: 10.2165/00003088-199834020-00003. [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
- Mano Y, Usui T, Kamimura H: The UDP-glucuronosyltransferase 2B7 isozyme is responsible for gemfibrozil glucuronidation in the human liver. Drug Metab Dispos. 2007 Nov;35(11):2040-4. doi: 10.1124/dmd.107.017269. Epub 2007 Aug 1. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- SubstrateInhibitor
- 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
- Gan J, Chen W, Shen H, Gao L, Hong Y, Tian Y, Li W, Zhang Y, Tang Y, Zhang H, Humphreys WG, Rodrigues AD: Repaglinide-gemfibrozil drug interaction: inhibition of repaglinide glucuronidation as a potential additional contributing mechanism. Br J Clin Pharmacol. 2010 Dec;70(6):870-80. doi: 10.1111/j.1365-2125.2010.03772.x. [Article]
- Williams JA, Hyland R, Jones BC, Smith DA, Hurst S, Goosen TC, Peterkin V, Koup JR, Ball SE: Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos. 2004 Nov;32(11):1201-8. doi: 10.1124/dmd.104.000794. Epub 2004 Aug 10. [Article]
- Mano Y, Usui T, Kamimura H: The UDP-glucuronosyltransferase 2B7 isozyme is responsible for gemfibrozil glucuronidation in the human liver. Drug Metab Dispos. 2007 Nov;35(11):2040-4. doi: 10.1124/dmd.107.017269. Epub 2007 Aug 1. [Article]
- FDA Label - ONIVYDE™ (irinotecan liposome injection) [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- 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
- Gill KL, Houston JB, Galetin A: Characterization of in vitro glucuronidation clearance of a range of drugs in human kidney microsomes: comparison with liver and intestinal glucuronidation and impact of albumin. Drug Metab Dispos. 2012 Apr;40(4):825-35. doi: 10.1124/dmd.111.043984. Epub 2012 Jan 24. [Article]
- Gan J, Chen W, Shen H, Gao L, Hong Y, Tian Y, Li W, Zhang Y, Tang Y, Zhang H, Humphreys WG, Rodrigues AD: Repaglinide-gemfibrozil drug interaction: inhibition of repaglinide glucuronidation as a potential additional contributing mechanism. Br J Clin Pharmacol. 2010 Dec;70(6):870-80. doi: 10.1111/j.1365-2125.2010.03772.x. [Article]
- Hirvensalo P, Tornio A, Neuvonen M, Tapaninen T, Paile-Hyvarinen M, Karja V, Mannisto VT, Pihlajamaki J, Backman JT, Niemi M: Comprehensive Pharmacogenomic Study Reveals an Important Role of UGT1A3 in Montelukast Pharmacokinetics. Clin Pharmacol Ther. 2018 Jul;104(1):158-168. doi: 10.1002/cpt.891. Epub 2017 Nov 6. [Article]
- Mano Y, Usui T, Kamimura H: The UDP-glucuronosyltransferase 2B7 isozyme is responsible for gemfibrozil glucuronidation in the human liver. Drug Metab Dispos. 2007 Nov;35(11):2040-4. doi: 10.1124/dmd.107.017269. Epub 2007 Aug 1. [Article]
- DRUG-DRUG INTERACTIONS – FROM KNOWLEDGE BASE TO CLINICAL IMPACT [File]
- The UDP-Glucuronosyltransferase 2B7 Isozyme Is Responsible for Gemfibrozil Glucuronidation in the Human Liver [File]
- 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:15470161, PubMed:15472229, PubMed:18004212, PubMed:18052087, PubMed:18674515, PubMed:19545173). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:12181437, PubMed:18004212). Catalyzes the glucuronidation of endogenous estrogen hormones such as estradiol and estrone (PubMed:15472229). Also catalyzes the glucuronidation of 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 caderastan, 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:20610558). Also metabolizes mycophenolate, an immunosuppressive agent (PubMed:15470161, PubMed:18004212)
- Specific Function
- enzyme binding
- Gene Name
- UGT1A9
- Uniprot ID
- O60656
- Uniprot Name
- UDP-glucuronosyltransferase 1A9
- Molecular Weight
- 59940.495 Da
References
- Mano Y, Usui T, Kamimura H: The UDP-glucuronosyltransferase 2B7 isozyme is responsible for gemfibrozil glucuronidation in the human liver. Drug Metab Dispos. 2007 Nov;35(11):2040-4. doi: 10.1124/dmd.107.017269. Epub 2007 Aug 1. [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:18719240, PubMed:23288867). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:18719240, PubMed:23288867). Catalyzes the glucuronidation of the endogenous estrogen hormones such as estradiol and estriol (PubMed:18719240, PubMed:23288867)
- Specific Function
- glucuronosyltransferase activity
- Gene Name
- UGT2B4
- Uniprot ID
- P06133
- Uniprot Name
- UDP-glucuronosyltransferase 2B4
- Molecular Weight
- 60512.035 Da
References
- Mano Y, Usui T, Kamimura H: The UDP-glucuronosyltransferase 2B7 isozyme is responsible for gemfibrozil glucuronidation in the human liver. Drug Metab Dispos. 2007 Nov;35(11):2040-4. doi: 10.1124/dmd.107.017269. Epub 2007 Aug 1. [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:19022937, PubMed:23288867, PubMed:8798464). Catalyzes the glucuronidation of endogenous steroid hormones such as androgens (epitestosterone, androsterone) and estrogens (estradiol, epiestradiol) (PubMed:16595710, PubMed:18719240, PubMed:19022937, PubMed:23288867, PubMed:8798464)
- Specific Function
- glucuronosyltransferase activity
- Gene Name
- UGT2B17
- Uniprot ID
- O75795
- Uniprot Name
- UDP-glucuronosyltransferase 2B17
- Molecular Weight
- 61094.915 Da
References
- Mano Y, Usui T, Kamimura H: The UDP-glucuronosyltransferase 2B7 isozyme is responsible for gemfibrozil glucuronidation in the human liver. Drug Metab Dispos. 2007 Nov;35(11):2040-4. doi: 10.1124/dmd.107.017269. Epub 2007 Aug 1. [Article]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- General Function
- Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transporter in plasma, typically binds about 80% of all plasma zinc (PubMed:19021548). Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity). Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity). Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli (PubMed:6234017). Does not prevent iron uptake by the bacterial siderophore aerobactin (PubMed:6234017)
- Specific Function
- antioxidant activity
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Albumin
- Molecular Weight
- 69365.94 Da
References
- Sallustio BC, Fairchild BA, Pannall PR: Interaction of human serum albumin with the electrophilic metabolite 1-O-gemfibrozil-beta-D-glucuronide. Drug Metab Dispos. 1997 Jan;25(1):55-60. [Article]
- Hamberger C, Barre J, Zini R, Taiclet A, Houin G, Tillement JP: In vitro binding study of gemfibrozil to human serum proteins and erythrocytes: interactions with other drugs. Int J Clin Pharmacol Res. 1986;6(6):441-9. [Article]
Drug created at June 13, 2005 13:24 / Updated at October 17, 2024 13:59