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Identification
- Summary
Repaglinide is a antihyperglycemic used to improve glycemic control in diabetes.
- Brand Names
- Enyglid, Gluconorm, Prandin
- Generic Name
- Repaglinide
- DrugBank Accession Number
- DB00912
- Background
Repaglinide is an oral antihyperglycemic agent used for the treatment of non-insulin-dependent diabetes mellitus (NIDDM). It belongs to the meglitinide class of short-acting insulin secretagogues, which act by binding to β cells of the pancreas to stimulate insulin release. Repaglinide induces an early insulin response to meals decreasing postprandial blood glucose levels. It should only be taken with meals and meal-time doses should be skipped with any skipped meal. Approximately one month of therapy is required before a decrease in fasting blood glucose is seen. Meglitnides may have a neutral effect on weight or cause a slight increase in weight. The average weight gain caused by meglitinides appears to be lower than that caused by sulfonylureas and insulin and appears to occur only in those naïve to oral antidiabetic agents. Due to their mechanism of action, meglitinides may cause hypoglycemia although the risk is thought to be lower than that of sulfonylureas since their action is dependent on the presence of glucose. In addition to reducing postprandial and fasting blood glucose, meglitnides have been shown to decrease glycosylated hemoglobin (HbA1c) levels, which are reflective of the last 8-10 weeks of glucose control. Meglitinides appear to be more effective at lowering postprandial blood glucose than metformin, sulfonylureas and thiazolidinediones. Repaglinide is extensively metabolized in the liver and excreted in bile. Repaglinide metabolites do not possess appreciable hypoglycemic activity. Approximately 90% of a single orally administered dose is eliminated in feces and 8% in urine.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Repaglinide (DB00912)
- Weight
- Average: 452.5857
Monoisotopic: 452.26750765 - Chemical Formula
- C27H36N2O4
- Synonyms
- Repaglinida
- Repaglinide
- Repaglinidum
- External IDs
- AG-EE 388 ZW
- AG-EE 623 ZW
- AG-EE-623ZW
Pharmacology
- Indication
As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used as adjunct in combination to manage Type 2 diabetes mellitus Combination Product in combination with: Metformin (DB00331) •••••••••••• Management of Type 2 diabetes mellitus •••••••••••• - Contraindications & Blackbox Warnings
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Insulin secretion by pancreatic β cells is partly controlled by cellular membrane potential. Membrane potential is regulated through an inverse relationship between the activity of cell membrane ATP-sensitive potassium channels (ABCC8) and extracellular glucose concentrations. Extracellular glucose enters the cell via GLUT2 (SLC2A2) transporters. Once inside the cell, glucose is metabolized to produce ATP. High concentrations of ATP inhibit ATP-sensitive potassium channels causing membrane depolarization. When extracellular glucose concentrations are low, ATP-sensitive potassium channels open causing membrane repolarization. High glucose concentrations cause ATP-sensitive potassium channels to close resulting in membrane depolarization and opening of L-type calcium channels. The influx of calcium ions stimulates calcium-dependent exocytosis of insulin granules. Repaglinide increases insulin release by inhibiting ATP-sensitive potassium channels in a glucose-dependent manner.
- Mechanism of action
Repaglinide activity is dependent on the presence functioning β cells and glucose. In contrast to sulfonylurea insulin secretatogogues, repaglinide has no effect on insulin release in the absence of glucose. Rather, it potentiates the effect of extracellular glucose on ATP-sensitive potassium channel and has little effect on insulin levels between meals and overnight. As such, repaglinide is more effective at reducing postprandial blood glucose levels than fasting blood glucose levels and requires a longer duration of therapy (approximately one month) before decreases in fasting blood glucose are observed. The insulinotropic effects of repaglinide are highest at intermediate glucose levels (3 to 10 mmol/L) and it does not increase insulin release already stimulated by high glucose concentrations (greater than 15 mmol/L). Repaglinide appears to be selective for pancreatic β cells and does not appear to affect skeletal or cardiac muscle or thyroid tissue.
Target Actions Organism AATP-binding cassette sub-family C member 9 blockerHumans AATP-binding cassette sub-family C member 8 inhibitorHumans AHistamine H1 receptor antagonistHumans UPeroxisome proliferator-activated receptor gamma agonistHumans - Absorption
Rapidly and completely absorbed following oral administration. Peak plasma concentrations are observed within 1 hour (range 0.5-1.4 hours). The absolute bioavailability is approximately 56%. Maximal biological effect is observed within 3-3.5 hours and plasma insulin levels remain elevated for 4-6 hours. When a single 2 mg dose of repaglinide is given to healthy subjects, the area under the curve (AUC) is 18.0 - 18.7 (ng/mL/h)^3.
- Volume of distribution
31 L following IV administration in healthy individuals
- Protein binding
>98% (e.g. to to albumin and α1-acid glycoprotein)
- Metabolism
Repaglinide is rapidly metabolized via oxidation and dealkylation by cytochrome P450 3A4 and 2C9 to form the major dicarboxylic acid derivative (M2). Further oxidation produces the aromatic amine derivative (M1). Glucuronidation of the carboxylic acid group of repaglinide yields an acyl glucuronide (M7). Several other unidentified metabolites have been detected. Repaglinide metabolites to not possess appreciable hypoglycemic activity.
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- Route of elimination
90% eliminated in feces (<2% as unchanged drug), 8% in urine (0.1% as unchanged drug)
- Half-life
1 hour
- Clearance
33-38 L/hour following IV administration
- Adverse Effects
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LD50 >1 g/kg (rat) (W. Grell)
- Pathways
Pathway Category Repaglinide Action Pathway Drug action - 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 softwareAbametapir The serum concentration of Repaglinide can be increased when it is combined with Abametapir. Abatacept The metabolism of Repaglinide can be increased when combined with Abatacept. Abiraterone The metabolism of Repaglinide can be decreased when combined with Abiraterone. Acarbose The risk or severity of hypoglycemia can be increased when Acarbose is combined with Repaglinide. Acebutolol The therapeutic efficacy of Repaglinide can be increased when used in combination with Acebutolol. - Food Interactions
- Take before a meal. Repaglinide should be taken before each meal of the day.
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
- GlucoNorm (Novo Nordisk) / Surepost
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Act Repaglinide Tablet 2 mg Oral Teva Italia S.R.L. 2010-10-18 Not applicable Canada 
Act Repaglinide Tablet 1 mg Oral Teva Italia S.R.L. 2010-10-18 Not applicable Canada Act Repaglinide Tablet 0.5 mg Oral Teva Italia S.R.L. 2010-10-18 Not applicable Canada Enyglid Tablet 1 mg Oral Krka D D., Novo Mesto 2016-09-08 Not applicable EU 
Enyglid Tablet 1 mg Oral Krka D D., Novo Mesto 2016-09-08 Not applicable EU - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Apo-repaglinide Tablet 2.0 mg Oral Apotex Corporation 2012-10-16 Not applicable Canada Apo-repaglinide Tablet 1.0 mg Oral Apotex Corporation 2012-10-16 Not applicable Canada Apo-repaglinide Tablet 0.5 mg Oral Apotex Corporation 2012-10-16 Not applicable Canada Auro-repaglinide Tablet 2 mg Oral Auro Pharma Inc 2014-04-30 Not applicable Canada Auro-repaglinide Tablet 1 mg Oral Auro Pharma Inc 2014-04-30 Not applicable Canada - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image PAREGLIN 1 MG/500 MG FILM KAPLI TABLET, 90 ADET Repaglinide (1 mg) + Metformin hydrochloride (500 mg) Tablet, film coated Oral İLKO İLAÇ SAN.VE TİC. A.Ş. 2015-09-14 Not applicable Turkey 
PAREGLIN 2 MG/500 MG FILM KAPLI TABLET, 90 ADET Repaglinide (2 mg) + Metformin hydrochloride (500 mg) Tablet, film coated Oral İLKO İLAÇ SAN.VE TİC. A.Ş. 2015-09-14 Not applicable Turkey Prandimet Repaglinide (2 mg/1) + Metformin hydrochloride (500 mg/1) Tablet Oral Novo Nordisk 2009-01-15 2017-05-31 US 
Prandimet Repaglinide (1 mg/1) + Metformin hydrochloride (500 mg/1) Tablet Oral Novo Nordisk 2009-01-16 2017-05-31 US Repaglinide and Metformin Hydrochloride Repaglinide (2 mg/1) + Metformin hydrochloride (500 mg/1) Tablet Oral Lupin Pharmaceuticals, Inc. 2015-12-10 2017-10-31 US
Categories
- ATC Codes
- A10BD14 — Metformin and repaglinide
- A10BD — Combinations of oral blood glucose lowering drugs
- A10B — BLOOD GLUCOSE LOWERING DRUGS, EXCL. INSULINS
- A10 — DRUGS USED IN DIABETES
- A — ALIMENTARY TRACT AND METABOLISM
- Drug Categories
- Acids, Acyclic
- Alimentary Tract and Metabolism
- Blood Glucose Lowering Agents
- BSEP/ABCB11 Substrates
- Cytochrome P-450 CYP2C8 Substrates
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- Drugs Used in Diabetes
- Glinide
- Hypoglycemia-Associated Agents
- Insulin Secretagogues
- Meglitinides
- OATP1B1/SLCO1B1 Substrates
- Oral Hypoglycemics
- Potassium Channel Blockers
- Stereoisomerism
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as phenylpiperidines. These are compounds containing a phenylpiperidine skeleton, which consists of a piperidine bound to a phenyl group.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Piperidines
- Sub Class
- Phenylpiperidines
- Direct Parent
- Phenylpiperidines
- Alternative Parents
- Phenylacetamides / Benzoic acids / Aniline and substituted anilines / Benzoyl derivatives / Dialkylarylamines / Phenol ethers / Phenoxy compounds / Alkyl aryl ethers / Amino acids / Secondary carboxylic acid amides show 7 more
- Substituents
- Alkyl aryl ether / Amine / Amino acid / Amino acid or derivatives / Aniline or substituted anilines / Aromatic heteromonocyclic compound / Azacycle / Benzenoid / Benzoic acid / Benzoic acid or derivatives show 23 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- piperidines (CHEBI:8805)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 668Z8C33LU
- CAS number
- 135062-02-1
- InChI Key
- FAEKWTJYAYMJKF-QHCPKHFHSA-N
- InChI
- InChI=1S/C27H36N2O4/c1-4-33-25-17-20(12-13-22(25)27(31)32)18-26(30)28-23(16-19(2)3)21-10-6-7-11-24(21)29-14-8-5-9-15-29/h6-7,10-13,17,19,23H,4-5,8-9,14-16,18H2,1-3H3,(H,28,30)(H,31,32)/t23-/m0/s1
- IUPAC Name
- 2-ethoxy-4-({[(1S)-3-methyl-1-[2-(piperidin-1-yl)phenyl]butyl]carbamoyl}methyl)benzoic acid
- SMILES
- CCOC1=C(C=CC(CC(=O)N[C@@H](CC(C)C)C2=CC=CC=C2N2CCCCC2)=C1)C(O)=O
References
- Synthesis Reference
Manne Reddy, "Polymorphic forms of (S)-Repaglinide and the processes for preparation thereof." U.S. Patent US20040102477, issued May 27, 2004.
US20040102477- General References
- External Links
- Human Metabolome Database
- HMDB0015048
- KEGG Drug
- D00594
- KEGG Compound
- C07670
- PubChem Compound
- 65981
- PubChem Substance
- 46508150
- ChemSpider
- 59377
- BindingDB
- 50153520
- 73044
- ChEBI
- 8805
- ChEMBL
- CHEMBL1272
- ZINC
- ZINC000003798537
- Therapeutic Targets Database
- DAP000133
- PharmGKB
- PA451234
- PDBe Ligand
- BJX
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- PDRhealth
- PDRhealth Drug Page
- Wikipedia
- Repaglinide
- PDB Entries
- 6jb1 / 6jb3 / 6pz9 / 7tys / 7tyt / 7u1q / 7u1s / 7y1j / 7y1k / 7y1l … show 2 more
- FDA label
- Download (175 KB)
- MSDS
- Download (57.3 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 Diabetes / Type 2 Diabetes Mellitus 6 somestatus stop reason just information to hide Not Available Completed Not Available Type 2 Diabetes Mellitus 3 somestatus stop reason just information to hide Not Available Completed Other Diabetes Related Cystic Fibrosis / Pancreatic Insufficiency 1 somestatus stop reason just information to hide Not Available Completed Treatment Diabetes 1 somestatus stop reason just information to hide Not Available Not Yet Recruiting Basic Science Drug Drug Interaction (DDI) 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Novo nordisk inc
- Novo Nordisk Inc.
- Packagers
- Boehringer Ingelheim Ltd.
- Cardinal Health
- Kaiser Foundation Hospital
- Lake Erie Medical and Surgical Supply
- Novo Nordisk Inc.
- Recipharm AB
- Dosage Forms
Form Route Strength Tablet Oral 0.5 mg Tablet Oral 1 mg Tablet Oral 2 mg Tablet Oral 1.0 mg Tablet Oral 2.0 mg Capsule, coated Oral 0.5 mg Tablet Oral 1 mg/tablet Tablet Oral 2 mg/tablet Tablet, film coated Oral Tablet Oral Tablet Oral Tablet Oral 0.5 mg/1 Tablet Oral 1 mg/1 Tablet Oral 2 mg/1 Tablet, effervescent Tablet Oral 4 mg Tablet Oral 0.50 mg Tablet, effervescent Oral - Prices
Unit description Cost Unit Prandin 1 mg tablet 2.48USD tablet Prandin 0.5 mg tablet 2.47USD tablet Prandin 2 mg tablet 2.33USD tablet Gluconorm 2 mg Tablet 0.34USD tablet Gluconorm 1 mg Tablet 0.32USD tablet Gluconorm 0.5 mg Tablet 0.31USD 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 US6677358 No 2004-01-13 2018-06-12 US CA2111851 No 2002-02-26 2011-06-21 Canada
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 130-131 °C Not Available logP 5.9 Not Available - Predicted Properties
Property Value Source Water Solubility 0.00294 mg/mL ALOGPS logP 5.05 ALOGPS logP 3.95 Chemaxon logS -5.2 ALOGPS pKa (Strongest Acidic) 3.68 Chemaxon pKa (Strongest Basic) 4.82 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 78.87 Å2 Chemaxon Rotatable Bond Count 10 Chemaxon Refractivity 131.83 m3·mol-1 Chemaxon Polarizability 51.49 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9172 Blood Brain Barrier - 0.7101 Caco-2 permeable - 0.5891 P-glycoprotein substrate Substrate 0.8145 P-glycoprotein inhibitor I Inhibitor 0.6044 P-glycoprotein inhibitor II Inhibitor 0.6868 Renal organic cation transporter Non-inhibitor 0.849 CYP450 2C9 substrate Non-substrate 0.8288 CYP450 2D6 substrate Non-substrate 0.9117 CYP450 3A4 substrate Substrate 0.7019 CYP450 1A2 substrate Non-inhibitor 0.9206 CYP450 2C9 inhibitor Non-inhibitor 0.907 CYP450 2D6 inhibitor Non-inhibitor 0.9231 CYP450 2C19 inhibitor Non-inhibitor 0.9026 CYP450 3A4 inhibitor Non-inhibitor 0.9264 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8682 Ames test Non AMES toxic 0.8136 Carcinogenicity Non-carcinogens 0.8004 Biodegradation Not ready biodegradable 0.919 Rat acute toxicity 2.4497 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9605 hERG inhibition (predictor II) Non-inhibitor 0.5272
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 233.2199722 predictedDarkChem Lite v0.1.0 [M-H]- 234.0079722 predictedDarkChem Lite v0.1.0 [M-H]- 207.23181 predictedDeepCCS 1.0 (2019) [M+H]+ 232.1213722 predictedDarkChem Lite v0.1.0 [M+H]+ 232.2016722 predictedDarkChem Lite v0.1.0 [M+H]+ 209.62738 predictedDeepCCS 1.0 (2019) [M+Na]+ 232.6062722 predictedDarkChem Lite v0.1.0 [M+Na]+ 232.5770722 predictedDarkChem Lite v0.1.0 [M+Na]+ 215.53992 predictedDeepCCS 1.0 (2019)
Targets
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Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Blocker
- General Function
- Subunit of ATP-sensitive potassium channels (KATP). Can form cardiac and smooth muscle-type KATP channels with KCNJ11. KCNJ11 forms the channel pore while ABCC9 is required for activation and regulation
- Specific Function
- ABC-type transporter activity
- Gene Name
- ABCC9
- Uniprot ID
- O60706
- Uniprot Name
- ATP-binding cassette sub-family C member 9
- Molecular Weight
- 174221.7 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
- Yes
- Actions
- Inhibitor
- General Function
- Subunit of the beta-cell ATP-sensitive potassium channel (KATP). Regulator of ATP-sensitive K(+) channels and insulin release
- Specific Function
- ABC-type transporter activity
- Gene Name
- ABCC8
- Uniprot ID
- Q09428
- Uniprot Name
- ATP-binding cassette sub-family C member 8
- Molecular Weight
- 176990.36 Da
References
- Hu S, Wang S, Fanelli B, Bell PA, Dunning BE, Geisse S, Schmitz R, Boettcher BR: Pancreatic beta-cell K(ATP) channel activity and membrane-binding studies with nateglinide: A comparison with sulfonylureas and repaglinide. J Pharmacol Exp Ther. 2000 May;293(2):444-52. [Article]
- Sunaga Y, Gonoi T, Shibasaki T, Ichikawa K, Kusama H, Yano H, Seino S: The effects of mitiglinide (KAD-1229), a new anti-diabetic drug, on ATP-sensitive K+ channels and insulin secretion: comparison with the sulfonylureas and nateglinide. Eur J Pharmacol. 2001 Nov 9;431(1):119-25. [Article]
- Hansen AM, Christensen IT, Hansen JB, Carr RD, Ashcroft FM, Wahl P: Differential interactions of nateglinide and repaglinide on the human beta-cell sulphonylurea receptor 1. Diabetes. 2002 Sep;51(9):2789-95. [Article]
- Wangler B, Schneider S, Thews O, Schirrmacher E, Comagic S, Feilen P, Schwanstecher C, Schwanstecher M, Shiue CY, Alavi A, Hohnemann S, Piel M, Rosch F, Schirrmacher R: Synthesis and evaluation of (S)-2-(2-[18F]fluoroethoxy)-4-([3-methyl-1-(2-piperidin-1-yl-phenyl)-butyl-carbam oyl]-methyl)-benzoic acid ([18F]repaglinide): a promising radioligand for quantification of pancreatic beta-cell mass with positron emission tomography (PET). Nucl Med Biol. 2004 Jul;31(5):639-47. [Article]
- Wangler B, Beck C, Shiue CY, Schneider S, Schwanstecher C, Schwanstecher M, Feilen PJ, Alavi A, Rosch F, Schirrmacher R: Synthesis and in vitro evaluation of (S)-2-([11C]methoxy)-4-[3-methyl-1-(2-piperidine-1-yl-phenyl)-butyl-carbamoyl]-be nzoic acid ([11C]methoxy-repaglinide): a potential beta-cell imaging agent. Bioorg Med Chem Lett. 2004 Oct 18;14(20):5205-9. [Article]
- Dornhorst A: Insulinotropic meglitinide analogues. Lancet. 2001 Nov 17;358(9294):1709-16. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- G-protein-coupled receptor for histamine, a biogenic amine that functions as an immune modulator and a neurotransmitter (PubMed:33828102, PubMed:8280179). Through the H1 receptor, histamine mediates the contraction of smooth muscles and increases capillary permeability due to contraction of terminal venules. Also mediates neurotransmission in the central nervous system and thereby regulates circadian rhythms, emotional and locomotor activities as well as cognitive functions (By similarity)
- Specific Function
- G protein-coupled serotonin receptor activity
- Gene Name
- HRH1
- Uniprot ID
- P35367
- Uniprot Name
- Histamine H1 receptor
- Molecular Weight
- 55783.61 Da
References
- Horak F, Unkauf M, Beckers C, Mittermaier EM: Efficacy and tolerability of intranasally applied dimetindene maleate solution versus placebo in the treatment of seasonal allergic rhinitis. Arzneimittelforschung. 2000 Dec;50(12):1099-105. doi: 10.1055/s-0031-1300341. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Agonist
- General Function
- Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE) and modulates the transcription of its target genes, such as acyl-CoA oxidase. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis. ARF6 acts as a key regulator of the tissue-specific adipocyte P2 (aP2) enhancer. Acts as a critical regulator of gut homeostasis by suppressing NF-kappa-B-mediated pro-inflammatory responses. Plays a role in the regulation of cardiovascular circadian rhythms by regulating the transcription of BMAL1 in the blood vessels (By similarity)
- Specific Function
- alpha-actinin binding
- Gene Name
- PPARG
- Uniprot ID
- P37231
- Uniprot Name
- Peroxisome proliferator-activated receptor gamma
- Molecular Weight
- 57619.58 Da
References
- Scarsi M, Podvinec M, Roth A, Hug H, Kersten S, Albrecht H, Schwede T, Meyer UA, Rucker C: Sulfonylureas and glinides exhibit peroxisome proliferator-activated receptor gamma activity: a combined virtual screening and biological assay approach. Mol Pharmacol. 2007 Feb;71(2):398-406. Epub 2006 Nov 2. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- 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
- Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
- Bidstrup TB, Bjornsdottir I, Sidelmann UG, Thomsen MS, Hansen KT: CYP2C8 and CYP3A4 are the principal enzymes involved in the human in vitro biotransformation of the insulin secretagogue repaglinide. Br J Clin Pharmacol. 2003 Sep;56(3):305-14. [Article]
- Flockhart Table of Drug Interactions [Link]
- 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
- Bidstrup TB, Bjornsdottir I, Sidelmann UG, Thomsen MS, Hansen KT: CYP2C8 and CYP3A4 are the principal enzymes involved in the human in vitro biotransformation of the insulin secretagogue repaglinide. Br J Clin Pharmacol. 2003 Sep;56(3):305-14. [Article]
- Kajosaari LI, Laitila J, Neuvonen PJ, Backman JT: Metabolism of repaglinide by CYP2C8 and CYP3A4 in vitro: effect of fibrates and rifampicin. Basic Clin Pharmacol Toxicol. 2005 Oct;97(4):249-56. doi: 10.1111/j.1742-7843.2005.pto_157.x. [Article]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- 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
Transporters
- 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
- He J, Qiu Z, Li N, Yu Y, Lu Y, Han D, Li T, Zhao D, Sun W, Fang F, Zheng J, Fan H, Chen X: Effects of SLCO1B1 polymorphisms on the pharmacokinetics and pharmacodynamics of repaglinide in healthy Chinese volunteers. Eur J Clin Pharmacol. 2011 Jul;67(7):701-7. doi: 10.1007/s00228-011-0994-7. Epub 2011 Feb 17. [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 21, 2024 08:50