Eluxadoline
Explore a selection of our essential drug information below, or:
Identification
- Summary
Eluxadoline is a mixed mu-opioid receptor agonist used to treat irritable bowel syndrome with diarrhea.
- Brand Names
- Viberzi
- Generic Name
- Eluxadoline
- DrugBank Accession Number
- DB09272
- Background
Eluxadoline is a mixed mu-opioid receptor agonist, kappa-opioid receptor agonist, and a-delta opioid receptor antagonist indicated for use in diarrhea-predominant irritable bowel syndrome (IBS-D). The mu-, kappa-, and delta-opioid receptors mediate endogenous and exogenous opioid response in the central nervous system and peripherally in the gastrointestinal system. Agonism of peripheral mu-opioid receptors results in reduced colonic motility, while antagonism of central delta-opioid receptors results in improved analgesia, making eluxadoline usable for the symptoms of both pain and diarrhea characteristic of IBS-D.
Marketed under the tradename Viberzi (FDA), eluxadoline is an antimotility agent that decreases bowel contractions, inhibits colonic transit, and reduces fluid/ion secretion resulting in improved symptoms of abdominal pain and reductions in the Bristol Stool Scale.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
- Weight
- Average: 569.662
Monoisotopic: 569.263819247 - Chemical Formula
- C32H35N5O5
- Synonyms
- 5-({(4-carbamoyl-2,6-dimethyl-L-phenylalanyl)[(1S)-1-(4-phenyl-1H-imidazol-2-yl)ethyl]amino}methyl)-2-methoxybenzoic acid
- Eluxadoline
- External IDs
- JNJ 27018966
- JNJ-27018966
- JNJ27018966
Pharmacology
- Indication
For the treatment of irritable bowel syndrome with diarrhea (IBS-D).
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 Management of Irritable bowel syndrome with diarrhea •••••••••••• - 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
Not Available
- Mechanism of action
Eluxadoline is a mu-opioid receptor agonis, kappa opioid receptor agonist and a delta opioid receptor antagonist. Eluxadoline is used for diarrhea predominant IBS because it reduces intestinal contractility and normalizes stress-induced acceleration of upper GI transit. Antagonistic activity at the delta receptor minimizes the constipating effect usually seen by mu-opioid receptor agonists alone. Because of it's limited systemic bioavailability, there may be less side effects associated with the use of eluxadoline in comparison with other therapies used to treat diarrhea predominant IBS.
Target Actions Organism AMu-type opioid receptor agonistHumans ADelta-type opioid receptor antagonistHumans AKappa-type opioid receptor agonistHumans - Absorption
The oral absorption of eluxadoline is poor - estimated to be 1.02%, this could be attributed to poor in vitro GI permeability, and its zwitterionic nature leading to a negatively charged molecule across the GI pH range.
- Volume of distribution
Not Available
- Protein binding
81%
- Metabolism
The metabolism of eluxadoline is currently unclear, however evidence suggests limited glucoronidation forms an acyl glucuronide metabolite that is then excreted into urine.
- Route of elimination
82% excreted in feces, <1% excreted in urine.
- Half-life
The mean plasma elimination half-life ranged from 3.7 hours to 6 hours.
- Clearance
Not Available
- 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 most common adverse reactions (>5%) are constipation, nausea and abdominal pain.
- 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 software1,2-Benzodiazepine The risk or severity of adverse effects can be increased when Eluxadoline is combined with 1,2-Benzodiazepine. Acetazolamide The therapeutic efficacy of Acetazolamide can be decreased when used in combination with Eluxadoline. Acetophenazine The risk or severity of hypotension and CNS depression can be increased when Acetophenazine is combined with Eluxadoline. Acetylcysteine The serum concentration of Eluxadoline can be increased when it is combined with Acetylcysteine. Acetylsalicylic acid The excretion of Eluxadoline can be decreased when combined with Acetylsalicylic acid. - Food Interactions
- Avoid excessive or chronic alcohol consumption. The risk of pancreatitis is increased with excess/chronic alcohol consumption.
- Take with food.
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.
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Truberzi Tablet, film coated 100 mg Oral Allergan Pharmaceuticals International Limited 2020-12-16 2016-07-21 EU Truberzi Tablet, film coated 75 mg Oral Allergan Pharmaceuticals International Limited 2020-12-16 2016-07-21 EU Truberzi Tablet, film coated 100 mg Oral Allergan Pharmaceuticals International Limited 2020-12-16 2016-07-21 EU Truberzi Tablet, film coated 100 mg Oral Allergan Pharmaceuticals International Limited 2020-12-16 2016-07-21 EU Truberzi Tablet, film coated 75 mg Oral Allergan Pharmaceuticals International Limited 2020-12-16 2016-07-21 EU
Categories
- ATC Codes
- A07DA06 — Eluxadoline
- Drug Categories
- Alimentary Tract and Metabolism
- Amino Acids
- Amino Acids, Aromatic
- Amino Acids, Cyclic
- Amino Acids, Peptides, and Proteins
- Antidiarrheals, Intestinal Antiinflammatory/antiinfective Agents
- Antipropulsives
- Gastrointestinal Agents
- Miscellaneous GI Drugs
- Mixed Agonist / Antagonist Opioids
- mu-Opioid Receptor Agonist
- OAT3/SLC22A8 Substrates
- OATP1B1/SLCO1B1 Inhibitors
- OATP1B1/SLCO1B1 Substrates
- Opioid Antagonists
- Opioids
- Receptors, Opioid, delta, antagonists & inhibitors
- Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as phenylalanine and derivatives. These are compounds containing phenylalanine or a derivative thereof resulting from reaction of phenylalanine at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.
- Kingdom
- Organic compounds
- Super Class
- Organic acids and derivatives
- Class
- Carboxylic acids and derivatives
- Sub Class
- Amino acids, peptides, and analogues
- Direct Parent
- Phenylalanine and derivatives
- Alternative Parents
- Alpha amino acid amides / Phenylimidazoles / O-methoxybenzoic acids and derivatives / Amphetamines and derivatives / Benzamides / Benzoic acids / m-Xylenes / Benzoyl derivatives / Anisoles / Imidazolyl carboxylic acids and derivatives show 16 more
- Substituents
- 4-phenylimidazole / 5-phenylimidazole / Alkyl aryl ether / Alpha-amino acid amide / Amine / Amino acid / Amphetamine or derivatives / Anisole / Aralkylamine / Aromatic heteromonocyclic compound show 35 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- amino acid amide, imidazoles, benzamides, L-phenylalanine derivative, methoxybenzoic acid (CHEBI:85980)
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 45TPJ4MBQ1
- CAS number
- 864821-90-9
- InChI Key
- QFNHIDANIVGXPE-FNZWTVRRSA-N
- InChI
- InChI=1S/C32H35N5O5/c1-18-12-23(29(34)38)13-19(2)24(18)15-26(33)31(39)37(17-21-10-11-28(42-4)25(14-21)32(40)41)20(3)30-35-16-27(36-30)22-8-6-5-7-9-22/h5-14,16,20,26H,15,17,33H2,1-4H3,(H2,34,38)(H,35,36)(H,40,41)/t20-,26-/m0/s1
- IUPAC Name
- 5-{[(2S)-2-amino-3-(4-carbamoyl-2,6-dimethylphenyl)-N-[(1S)-1-(4-phenyl-1H-imidazol-2-yl)ethyl]propanamido]methyl}-2-methoxybenzoic acid
- SMILES
- COC1=CC=C(CN([C@@H](C)C2=NC(=CN2)C2=CC=CC=C2)C(=O)[C@@H](N)CC2=C(C)C=C(C=C2C)C(N)=O)C=C1C(O)=O
References
- Synthesis Reference
Breslin HJ, Diamond CJ, Kavash RW, Cai C, Dyatkin AB, Miskowski TA, Zhang SP, Wade PR, Hornby PJ, He W: Identification of a dual delta OR antagonist/mu OR agonist as a potential therapeutic for diarrhea-predominant Irritable Bowel Syndrome (IBS-d). Bioorg Med Chem Lett. 2012 Jul 15;22(14):4869-72. doi: 10.1016/j.bmcl.2012.05.042. Epub 2012 May 24. Pubmed
- General References
- Garnock-Jones KP: Eluxadoline: First Global Approval. Drugs. 2015 Jul;75(11):1305-10. doi: 10.1007/s40265-015-0436-4. [Article]
- Nee J, Zakari M, Lembo AJ: Current and emerging drug options in the treatment of diarrhea predominant irritable bowel syndrome. Expert Opin Pharmacother. 2015 Dec;16(18):2781-92. doi: 10.1517/14656566.2015.1101449. Epub 2015 Nov 11. [Article]
- Dove LS, Lembo A, Randall CW, Fogel R, Andrae D, Davenport JM, McIntyre G, Almenoff JS, Covington PS: Eluxadoline benefits patients with irritable bowel syndrome with diarrhea in a phase 2 study. Gastroenterology. 2013 Aug;145(2):329-38.e1. doi: 10.1053/j.gastro.2013.04.006. Epub 2013 Apr 9. [Article]
- Davenport JM, Covington P, Bonifacio L, McIntyre G, Venitz J: Effect of uptake transporters OAT3 and OATP1B1 and efflux transporter MRP2 on the pharmacokinetics of eluxadoline. J Clin Pharmacol. 2015 May;55(5):534-42. doi: 10.1002/jcph.442. Epub 2015 Jan 14. [Article]
- Fujita W, Gomes I, Dove LS, Prohaska D, McIntyre G, Devi LA: Molecular characterization of eluxadoline as a potential ligand targeting mu-delta opioid receptor heteromers. Biochem Pharmacol. 2014 Dec 1;92(3):448-56. doi: 10.1016/j.bcp.2014.09.015. Epub 2014 Sep 28. [Article]
- FDA Approved Drug Products: VIBERZI (eluxadoline) tablets [Link]
- External Links
- KEGG Drug
- D10403
- PubChem Compound
- 11250029
- PubChem Substance
- 310265167
- ChemSpider
- 9425062
- BindingDB
- 50393720
- 1653781
- ChEBI
- 85980
- ChEMBL
- CHEMBL2159122
- ZINC
- ZINC000014210876
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Eluxadoline
- FDA label
- Download (503 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 data4 Completed Treatment Diarrhoea Predominant Irritable Bowel Syndrome 2 somestatus stop reason just information to hide 3 Completed Treatment Irritable Bowel Syndrome (IBS) 2 somestatus stop reason just information to hide 3 Enrolling by Invitation Treatment Irritable Bowel Syndrome (IBS) 1 somestatus stop reason just information to hide 2 Completed Treatment Irritable Bowel Syndrome (IBS) 1 somestatus stop reason just information to hide 2 Recruiting Treatment Irritable Bowel Syndrome (IBS) 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet, film coated Oral 100 MG Tablet, film coated Oral 75 MG Tablet Oral 100 mg Tablet Oral 75 mg Tablet, film coated Oral 100 mg/1 Tablet, film coated Oral 75 mg/1 - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US9115091 No 2015-08-25 2028-07-07 US US9205076 No 2015-12-08 2025-03-14 US US8691860 No 2014-04-08 2028-07-07 US US8344011 No 2013-01-01 2025-03-14 US US8609709 No 2013-12-17 2025-03-14 US US7741356 No 2010-06-22 2028-03-25 US US7786158 No 2010-08-31 2025-03-14 US US9364489 No 2016-06-14 2028-07-07 US US8772325 No 2014-07-08 2025-03-14 US US9675587 No 2017-06-13 2033-03-14 US US9700542 No 2017-07-11 2025-03-14 US US9789125 No 2017-10-17 2028-07-07 US US10188632 No 2019-01-29 2033-03-14 US US10213415 No 2019-02-26 2025-03-14 US US11007179 No 2021-05-18 2033-03-14 US US11090291 No 2021-08-17 2033-03-14 US US11160792 No 2021-11-02 2033-03-14 US US11229627 No 2013-03-14 2033-03-14 US US11311516 No 2013-03-14 2033-03-14 US US11484527 No 2013-03-14 2033-03-14 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.00268 mg/mL ALOGPS logP 1.08 ALOGPS logP 1.8 Chemaxon logS -5.3 ALOGPS pKa (Strongest Acidic) 3.66 Chemaxon pKa (Strongest Basic) 7.99 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 7 Chemaxon Hydrogen Donor Count 4 Chemaxon Polar Surface Area 164.63 Å2 Chemaxon Rotatable Bond Count 11 Chemaxon Refractivity 160.38 m3·mol-1 Chemaxon Polarizability 61.86 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 266.7670883 predictedDarkChem Lite v0.1.0 [M-H]- 230.68307 predictedDeepCCS 1.0 (2019) [M+H]+ 266.0612883 predictedDarkChem Lite v0.1.0 [M+H]+ 232.50795 predictedDeepCCS 1.0 (2019) [M+Na]+ 267.0704883 predictedDarkChem Lite v0.1.0 [M+Na]+ 238.11378 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Receptor for endogenous opioids such as beta-endorphin and endomorphin (PubMed:10529478, PubMed:12589820, PubMed:7891175, PubMed:7905839, PubMed:7957926, PubMed:9689128). Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone (PubMed:10529478, PubMed:10836142, PubMed:12589820, PubMed:19300905, PubMed:7891175, PubMed:7905839, PubMed:7957926, PubMed:9689128). Also activated by enkephalin peptides, such as Met-enkephalin or Met-enkephalin-Arg-Phe, with higher affinity for Met-enkephalin-Arg-Phe (By similarity). Agonist binding to the receptor induces coupling to an inactive GDP-bound heterotrimeric G-protein complex and subsequent exchange of GDP for GTP in the G-protein alpha subunit leading to dissociation of the G-protein complex with the free GTP-bound G-protein alpha and the G-protein beta-gamma dimer activating downstream cellular effectors (PubMed:7905839). The agonist- and cell type-specific activity is predominantly coupled to pertussis toxin-sensitive G(i) and G(o) G alpha proteins, GNAI1, GNAI2, GNAI3 and GNAO1 isoforms Alpha-1 and Alpha-2, and to a lesser extent to pertussis toxin-insensitive G alpha proteins GNAZ and GNA15 (PubMed:12068084). They mediate an array of downstream cellular responses, including inhibition of adenylate cyclase activity and both N-type and L-type calcium channels, activation of inward rectifying potassium channels, mitogen-activated protein kinase (MAPK), phospholipase C (PLC), phosphoinositide/protein kinase (PKC), phosphoinositide 3-kinase (PI3K) and regulation of NF-kappa-B (By similarity). Also couples to adenylate cyclase stimulatory G alpha proteins (By similarity). The selective temporal coupling to G-proteins and subsequent signaling can be regulated by RGSZ proteins, such as RGS9, RGS17 and RGS4 (By similarity). Phosphorylation by members of the GPRK subfamily of Ser/Thr protein kinases and association with beta-arrestins is involved in short-term receptor desensitization (By similarity). Beta-arrestins associate with the GPRK-phosphorylated receptor and uncouple it from the G-protein thus terminating signal transduction (By similarity). The phosphorylated receptor is internalized through endocytosis via clathrin-coated pits which involves beta-arrestins (By similarity). The activation of the ERK pathway occurs either in a G-protein-dependent or a beta-arrestin-dependent manner and is regulated by agonist-specific receptor phosphorylation (By similarity). Acts as a class A G-protein coupled receptor (GPCR) which dissociates from beta-arrestin at or near the plasma membrane and undergoes rapid recycling (By similarity). Receptor down-regulation pathways are varying with the agonist and occur dependent or independent of G-protein coupling (By similarity). Endogenous ligands induce rapid desensitization, endocytosis and recycling (By similarity). Heterooligomerization with other GPCRs can modulate agonist binding, signaling and trafficking properties (By similarity)
- Specific Function
- beta-endorphin receptor activity
- Gene Name
- OPRM1
- Uniprot ID
- P35372
- Uniprot Name
- Mu-type opioid receptor
- Molecular Weight
- 44778.855 Da
References
- Fujita W, Gomes I, Dove LS, Prohaska D, McIntyre G, Devi LA: Molecular characterization of eluxadoline as a potential ligand targeting mu-delta opioid receptor heteromers. Biochem Pharmacol. 2014 Dec 1;92(3):448-56. doi: 10.1016/j.bcp.2014.09.015. Epub 2014 Sep 28. [Article]
- Dove LS, Lembo A, Randall CW, Fogel R, Andrae D, Davenport JM, McIntyre G, Almenoff JS, Covington PS: Eluxadoline benefits patients with irritable bowel syndrome with diarrhea in a phase 2 study. Gastroenterology. 2013 Aug;145(2):329-38.e1. doi: 10.1053/j.gastro.2013.04.006. Epub 2013 Apr 9. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- G-protein coupled receptor that functions as a receptor for endogenous enkephalins and for a subset of other opioids. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling leads to the inhibition of adenylate cyclase activity. Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Plays a role in the perception of pain and in opiate-mediated analgesia. Plays a role in developing analgesic tolerance to morphine
- Specific Function
- G protein-coupled enkephalin receptor activity
- Gene Name
- OPRD1
- Uniprot ID
- P41143
- Uniprot Name
- Delta-type opioid receptor
- Molecular Weight
- 40368.235 Da
References
- Fujita W, Gomes I, Dove LS, Prohaska D, McIntyre G, Devi LA: Molecular characterization of eluxadoline as a potential ligand targeting mu-delta opioid receptor heteromers. Biochem Pharmacol. 2014 Dec 1;92(3):448-56. doi: 10.1016/j.bcp.2014.09.015. Epub 2014 Sep 28. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- G-protein coupled opioid receptor that functions as a receptor for endogenous alpha-neoendorphins and dynorphins, but has low affinity for beta-endorphins. Also functions as a receptor for various synthetic opioids and for the psychoactive diterpene salvinorin A. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling leads to the inhibition of adenylate cyclase activity. Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Plays a role in the perception of pain. Plays a role in mediating reduced physical activity upon treatment with synthetic opioids. Plays a role in the regulation of salivation in response to synthetic opioids. May play a role in arousal and regulation of autonomic and neuroendocrine functions
- Specific Function
- dynorphin receptor activity
- Gene Name
- OPRK1
- Uniprot ID
- P41145
- Uniprot Name
- Kappa-type opioid receptor
- Molecular Weight
- 42644.665 Da
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- 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
- Davenport JM, Covington P, Bonifacio L, McIntyre G, Venitz J: Effect of uptake transporters OAT3 and OATP1B1 and efflux transporter MRP2 on the pharmacokinetics of eluxadoline. J Clin Pharmacol. 2015 May;55(5):534-42. doi: 10.1002/jcph.442. Epub 2015 Jan 14. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- ATP-dependent transporter of the ATP-binding cassette (ABC) family that binds and hydrolyzes ATP to enable active transport of various substrates including many drugs, toxicants and endogenous compound across cell membranes. Transports a wide variety of conjugated organic anions such as sulfate-, glucuronide- and glutathione (GSH)-conjugates of endo- and xenobiotics substrates (PubMed:10220572, PubMed:10421658, PubMed:11500505, PubMed:16332456). Mediates hepatobiliary excretion of mono- and bis-glucuronidated bilirubin molecules and therefore play an important role in bilirubin detoxification (PubMed:10421658). Mediates also hepatobiliary excretion of others glucuronide conjugates such as 17beta-estradiol 17-glucosiduronic acid and leukotriene C4 (PubMed:11500505). Transports sulfated bile salt such as taurolithocholate sulfate (PubMed:16332456). Transports various anticancer drugs, such as anthracycline, vinca alkaloid and methotrexate and HIV-drugs such as protease inhibitors (PubMed:10220572, PubMed:11500505, PubMed:12441801). Confers resistance to several anti-cancer drugs including cisplatin, doxorubicin, epirubicin, methotrexate, etoposide and vincristine (PubMed:10220572, PubMed:11500505)
- Specific Function
- ABC-type glutathione S-conjugate transporter activity
- Gene Name
- ABCC2
- Uniprot ID
- Q92887
- Uniprot Name
- ATP-binding cassette sub-family C member 2
- Molecular Weight
- 174205.64 Da
References
- Davenport JM, Covington P, Bonifacio L, McIntyre G, Venitz J: Effect of uptake transporters OAT3 and OATP1B1 and efflux transporter MRP2 on the pharmacokinetics of eluxadoline. J Clin Pharmacol. 2015 May;55(5):534-42. doi: 10.1002/jcph.442. Epub 2015 Jan 14. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- 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
- Davenport JM, Covington P, Bonifacio L, McIntyre G, Venitz J: Effect of uptake transporters OAT3 and OATP1B1 and efflux transporter MRP2 on the pharmacokinetics of eluxadoline. J Clin Pharmacol. 2015 May;55(5):534-42. doi: 10.1002/jcph.442. Epub 2015 Jan 14. [Article]
Drug created at October 28, 2015 19:50 / Updated at April 23, 2024 11:38