Rilpivirine
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Identification
- Summary
Rilpivirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) used in combination with other antiretrovirals to specifically treat human immunodeficiency virus type 1 (HIV-1).
- Brand Names
- Complera, Edurant, Juluca, Odefsey
- Generic Name
- Rilpivirine
- DrugBank Accession Number
- DB08864
- Background
Rilpivirine is non-nucleoside reverse transcriptase inhibitor (NNRTI) which is used for the treatment of HIV-1 infections in treatment-naive patients.1 It is a diarylpyrimidine derivative.2 The internal conformational flexibility of rilpivirine and the plasticity of it interacting binding site gives it a very high potency and reduces the chance of resistance compared to other NNRTI's.3 Rilpivirine was developed by Tilbotec, Inc. and FDA approved on May 20, 2011.6 On November 21, 2017, Rilpivirine, in combination with dolutegravir, was approved as part of the first complete treatment regimen with only two drugs for the treatment of adults with HIV-1 named Juluca.7 Rilpivirine in combination with cabotegravir was granted FDA approval on 21 January 2021.10 While previously administered once-monthly only, this combination product was granted FDA approval for dosing every two months on February 01, 2022 11 and without the need for an oral lead-in period prior.10
- Type
- Small Molecule
- Groups
- Approved
- Structure
- Weight
- Average: 366.4185
Monoisotopic: 366.159294606 - Chemical Formula
- C22H18N6
- Synonyms
- 4-{[4-({4-[(E)-2-cyanovinyl]-2,6-dimethylphenyl}amino)pyrimidin-2-yl]amino}benzonitrile
- Rilpivirina
- Rilpivirine
- External IDs
- R 278474
- R-278474
- R278474
- TMC 278
- TMC-278
- TMC278
Pharmacology
- Indication
Rilpivirine, in combination with other agents, is indicated for the treatment of HIV-1 infections in antiretroviral treatment-naive patients with HIV-1 RNA ≤100,000 copies/mL and CD4+ cell count >200 cells/mm3.6,13 The FDA combination therapy approval of rilpivirine and dolutegravir is indicated for adults and adolescents 12 years of age and older weighing at least 35 kg with HIV-1 infections whose virus is currently suppressed (< 50 copies/ml) on a stable regimen for at least six months, without a history of treatment failure and no known substitutions associated to resistance to any of the two components of the therapy.7
Rilpivirine in combination with cabotegravir is indicated as a complete regimen for the treatment of HIV-1 infection in adults and adolescents - ≥12 years old and weighing at least 35kg - to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable antiretroviral regimen with no history of treatment failure and with no known or suspected resistance to either cabotegravir or rilpivirine.10
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination to treat Hiv-1 infection •••••••••••• ••••••••• •••••• ••••• ••• •••• •••• •• ••••• •• ••••••• •••••••••• •••••• •• ••••• •• •• ••••••••••• •••••• Used in combination to treat Hiv-1 infection •••••••••••• •••••• •• ••••• •• ••• •••••••••••••••• ••••• ••• •••• •••• •• ••••• •• ••••••• ••••••••• •••••• Used in combination to treat Human immunodeficiency virus type 1 (hiv-1) Combination Product in combination with: Dolutegravir (DB08930) •••••••••••• ••••• ••• ••••• •••• ••••••••••••• •••••• •••••••••••••• •••••••• •• ••••••• •• ••••••••• ••••••• •••••• Used in combination to treat Human immunodeficiency virus type 1 (hiv-1) Combination Product in combination with: Cabotegravir (DB11751) •••••••••••• ••••••••••• ••••• •• ••••••• •• ••••••••• •••••••• •••••••••••••••••••••••• •••••• •• ••••• •• •• - 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
Rilpivirine is a non-nucleoside reverse transcriptase inhibitor that inhibits the replication of HIV-1.9 It has a long duration of action as the oral tablet is given daily and the intramuscular suspension is given monthly.9,10 Patients should be counselled regarding the risk of hypersensitivity reactions, hepatotoxicity, depressive disorders, and the redistribution or accumulation of body fat.9
- Mechanism of action
Rilpivirine is a non-competitive NNRTI that binds to reverse transcriptase.9 Its binding results in the blockage of RNA and DNA- dependent DNA polymerase activities, like HIV-1 replication. It does not present activity against human DNA polymerases α, β and γ.8,9 Rilpivirine's flexible structure around the aromatic rings allows the adaptation to changes in the non-nucleoside RT binding pocket, reducing the likelihood of viral mutations conferring resistance.4
Target Actions Organism AReverse transcriptase/RNaseH inhibitorHuman immunodeficiency virus 1 ASodium channel protein type 10 subunit alpha inhibitorHumans AGag-Pol polyprotein inhibitorUNuclear receptor subfamily 1 group I member 2 agonistHumans - Absorption
Rilpivirine has a Tmax of 3-4 hours and has a mean AUC of 2235 ± 851 ng*h/mL.3,9 A 25mg dose reaches a Cmax of 247 ng/mL in healthy subjects and 138.6 ng/mL in patients with HIV-1.8
- Volume of distribution
In HIV-1 patients, the apparent volume of distribution in the central compartment was 152-173 L.8
- Protein binding
Rilpivirine is >99% bound to plasma protein, most commonly albumin.3,9
- Metabolism
Rilpivirine is predominantly metabolized by CYP3A4 and CYP3A5 to the hydroxylated metabolites M1, M2, M3, and M4.5,9 UGT1A1 glucuronidates the M2 metabolite to form M6, UGT1A4 glucuronidates rilpivirine to form M5, and an unknown UGT glucuronidates the M4 metabolite to form M7.5
Hover over products below to view reaction partners
- Route of elimination
Rilpivirine is 85% eliminated in the feces and 6.1% eliminated in the urine.9 25% of a dose is recovered in the feces as the unchanged parent drug, while <1% of a dose is recovered in the urine as the unchanged parent drug.9
- Half-life
Rilpivirine has a terminal half-life of 34-55 hours.3
- Clearance
In HIV-1 patients, the apparent total clearance is estimated to be 6.89-8.66 L/h.8
- 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
In the event of an overdose, contact a poison control centre.9 Patients should be treated with symptomatic and supportive measures, including monitoring of the QT interval.9 Dialysis is not expected to remove significant amounts of the drug from plasma as it is highly bound to albumin.9
- 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 softwareAbametapir The serum concentration of Rilpivirine can be increased when it is combined with Abametapir. Abatacept The metabolism of Rilpivirine can be increased when combined with Abatacept. Abemaciclib The metabolism of Abemaciclib can be decreased when combined with Rilpivirine. Abrocitinib The metabolism of Abrocitinib can be decreased when combined with Rilpivirine. Acalabrutinib The serum concentration of Rilpivirine can be increased when it is combined with Acalabrutinib. - Food Interactions
- Avoid St. John's Wort. St.John's Wort will decrease levels of this medication.
- Take with food. Absorption is increased by 40% if taken 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.
- Product Ingredients
Ingredient UNII CAS InChI Key Rilpivirine hydrochloride 212WAX8KDD 700361-47-3 KZVVGZKAVZUACK-BJILWQEISA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Edurant Tablet, film coated 25 mg Oral Janssen Cilag International Nv 2016-09-08 Not applicable EU Edurant Tablet, film coated 25 mg/1 Oral Janssen Products, LP 2011-05-20 Not applicable US Edurant Tablet 25 mg Oral Janssen Pharmaceuticals 2011-08-31 Not applicable Canada Edurant Ped Tablet, for suspension 2.5 mg/1 Oral Janssen Products, LP 2024-03-15 Not applicable US Rekambys Injection 900 mg Intramuscular Janssen Cilag International Nv 2021-01-12 Not applicable EU - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Cabenuva Rilpivirine (300 mg/1mL) + Cabotegravir (200 mg/1mL) Injection, suspension, extended release; Kit Intramuscular ViiV Healthcare Company 2021-01-21 Not applicable US Cabenuva Rilpivirine (300 mg / mL) + Cabotegravir (200 mg / mL) Kit; Suspension, extended release Intramuscular Viiv Healthcare Bv 2020-09-21 Not applicable Canada Cabenuva Rilpivirine (300 mg / mL) + Cabotegravir (200 mg / mL) Kit; Suspension, extended release Intramuscular Viiv Healthcare Bv 2020-09-21 Not applicable Canada Cabenuva Rilpivirine (300 mg/1mL) + Cabotegravir (200 mg/1mL) Injection, suspension, extended release; Kit Intramuscular ViiV Healthcare Company 2021-01-21 Not applicable US Complera Rilpivirine hydrochloride (25 mg/1) + Emtricitabine (200 mg/1) + Tenofovir disoproxil fumarate (300 mg/1) Tablet, film coated Oral A-S Medication Solutions 2011-08-10 2019-01-31 US
Categories
- ATC Codes
- J05AR19 — Emtricitabine, tenofovir alafenamide and rilpivirine
- J05AR — Antivirals for treatment of HIV infections, combinations
- J05A — DIRECT ACTING ANTIVIRALS
- J05 — ANTIVIRALS FOR SYSTEMIC USE
- J — ANTIINFECTIVES FOR SYSTEMIC USE
- J05AR — Antivirals for treatment of HIV infections, combinations
- J05A — DIRECT ACTING ANTIVIRALS
- J05 — ANTIVIRALS FOR SYSTEMIC USE
- J — ANTIINFECTIVES FOR SYSTEMIC USE
- J05AR — Antivirals for treatment of HIV infections, combinations
- J05A — DIRECT ACTING ANTIVIRALS
- J05 — ANTIVIRALS FOR SYSTEMIC USE
- J — ANTIINFECTIVES FOR SYSTEMIC USE
- Drug Categories
- Anti-HIV Agents
- Anti-Infective Agents
- Anti-Retroviral Agents
- Antiinfectives for Systemic Use
- Antiviral Agents
- Antivirals for Systemic Use
- Antivirals used in combination for the treatment of HIV infections
- BCRP/ABCG2 Inhibitors
- Cytochrome P-450 CYP2B6 Inhibitors
- Cytochrome P-450 CYP2B6 Inhibitors (strong)
- Cytochrome P-450 CYP2C19 Inhibitors
- Cytochrome P-450 CYP2C19 inhibitors (strength unknown)
- Cytochrome P-450 CYP2C19 Substrates
- Cytochrome P-450 CYP2C8 Inhibitors
- Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2C9 Inhibitors
- Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2E1 Inhibitors
- Cytochrome P-450 CYP2E1 Inhibitors (strength unknown)
- Cytochrome P-450 CYP3A Inducers
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inducers
- Cytochrome P-450 CYP3A4 Inducers (strength unknown)
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (weak)
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Enzyme Inducers
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Direct Acting Antivirals
- Enzyme Inhibitors
- Human Immunodeficiency Virus 1 Non-Nucleoside Analog Reverse Transcriptase Inhibitor
- Nitriles
- Non-Nucleoside Reverse Transcriptase Inhibitors
- Nonnucleoside Reverse Transcriptase Inhibitors
- Nucleic Acid Synthesis Inhibitors
- OATP1B1/SLCO1B1 Inhibitors
- OATP1B3 inhibitors
- P-glycoprotein inhibitors
- Potential QTc-Prolonging Agents
- Pyrimidines
- QTc Prolonging Agents
- Reverse Transcriptase Inhibitors
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as benzonitriles. These are organic compounds containing a benzene bearing a nitrile substituent.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- Benzonitriles
- Direct Parent
- Benzonitriles
- Alternative Parents
- m-Xylenes / Styrenes / Aniline and substituted anilines / Aminopyrimidines and derivatives / Imidolactams / Hydropyrimidines / Heteroaromatic compounds / Secondary amines / Nitriles / Azacyclic compounds show 2 more
- Substituents
- Amine / Aminopyrimidine / Aniline or substituted anilines / Aromatic heteromonocyclic compound / Azacycle / Benzonitrile / Carbonitrile / Heteroaromatic compound / Hydrocarbon derivative / Hydropyrimidine show 11 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- aminopyrimidine, nitrile (CHEBI:68606)
- Affected organisms
- Humans and other mammals
- Human Immunodeficiency Virus
Chemical Identifiers
- UNII
- FI96A8X663
- CAS number
- 500287-72-9
- InChI Key
- YIBOMRUWOWDFLG-ONEGZZNKSA-N
- InChI
- InChI=1S/C22H18N6/c1-15-12-18(4-3-10-23)13-16(2)21(15)27-20-9-11-25-22(28-20)26-19-7-5-17(14-24)6-8-19/h3-9,11-13H,1-2H3,(H2,25,26,27,28)/b4-3+
- IUPAC Name
- 4-{[4-({4-[(1E)-2-cyanoeth-1-en-1-yl]-2,6-dimethylphenyl}amino)pyrimidin-2-yl]amino}benzonitrile
- SMILES
- CC1=CC(\C=C\C#N)=CC(C)=C1NC1=CC=NC(NC2=CC=C(C=C2)C#N)=N1
References
- General References
- Putcharoen O, Kerr SJ, Ruxrungtham K: An update on clinical utility of rilpivirine in the management of HIV infection in treatment-naive patients. HIV AIDS (Auckl). 2013 Sep 16;5:231-41. doi: 10.2147/HIV.S25712. [Article]
- Usach I, Melis V, Peris JE: Non-nucleoside reverse transcriptase inhibitors: a review on pharmacokinetics, pharmacodynamics, safety and tolerability. J Int AIDS Soc. 2013 Sep 4;16:1-14. doi: 10.7448/IAS.16.1.18567. [Article]
- Ford N, Lee J, Andrieux-Meyer I, Calmy A: Safety, efficacy, and pharmacokinetics of rilpivirine: systematic review with an emphasis on resource-limited settings. HIV AIDS (Auckl). 2011;3:35-44. doi: 10.2147/HIV.S14559. Epub 2011 Apr 28. [Article]
- Azijn H, Tirry I, Vingerhoets J, de Bethune MP, Kraus G, Boven K, Jochmans D, Van Craenenbroeck E, Picchio G, Rimsky LT: TMC278, a next-generation nonnucleoside reverse transcriptase inhibitor (NNRTI), active against wild-type and NNRTI-resistant HIV-1. Antimicrob Agents Chemother. 2010 Feb;54(2):718-27. doi: 10.1128/AAC.00986-09. Epub 2009 Nov 23. [Article]
- Lade JM, Avery LB, Bumpus NN: Human biotransformation of the nonnucleoside reverse transcriptase inhibitor rilpivirine and a cross-species metabolism comparison. Antimicrob Agents Chemother. 2013 Oct;57(10):5067-79. doi: 10.1128/AAC.01401-13. Epub 2013 Aug 5. [Article]
- J&J News [Link]
- FDA News and Events [Link]
- Australian Government: Australian Public Assessment Report for Rilpivirine [Link]
- FDA Approved Drug Products: Edurant (rilpivirine) oral tablets [Link]
- FDA Approved Drug Products: Cabenuva (Cabotegravir and Rilpivirine) Intramuscular Extended-Release Suspension [Link]
- BioSpace News: ViiV Healthcare Announces US FDA Approval of Cabenuva (cabotegravir, rilpivirine) for Use Every Two Months, Expanding the Label of the First and Only Complete Long-Acting HIV Treatment [Link]
- FDA Approved Drug Products: JULUCA (dolutegravir and rilpivirine tablets), for oral use [Link]
- FDA Approved Drug Products: EDURANT (rilpivirine) suspension or tablets, for oral use (March 2024) [Link]
- External Links
- Human Metabolome Database
- HMDB0061725
- KEGG Drug
- D09720
- PubChem Compound
- 6451164
- PubChem Substance
- 175427123
- ChemSpider
- 4953643
- BindingDB
- 222178
- 1102270
- ChEBI
- 68606
- ChEMBL
- CHEMBL175691
- ZINC
- ZINC000001554274
- PDBe Ligand
- T27
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Rilpivirine
- PDB Entries
- 2zd1 / 2ze2 / 3bgr / 3qlh / 4g1q / 4icl / 4id5 / 4idk / 4ifv / 4ify … show 19 more
- FDA label
- Download (558 KB)
- MSDS
- Download (568 KB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Active Not Recruiting Not Available Human Immunodeficiency Virus (HIV) Infections 1 somestatus stop reason just information to hide Not Available Approved for Marketing Not Available Human Immunodeficiency Virus (HIV) Infections 1 somestatus stop reason just information to hide Not Available Completed Not Available Acquired Immune Deficiency Syndrome (AIDS) 1 somestatus stop reason just information to hide Not Available Completed Not Available Coronavirus Disease 2019 (COVID‑19) / Human Immunodeficiency Virus (HIV) Infections 1 somestatus stop reason just information to hide Not Available Completed Not Available Human Immunodeficiency Virus (HIV) Infections 2 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, suspension, extended release; kit Intramuscular Kit; suspension, extended release Intramuscular Tablet, film coated Oral Tablet Oral 25 mg Tablet Oral 27.500 mg Tablet, coated Oral 25 mg Tablet, film coated Oral 25 mg/1 Tablet, film coated Oral 27.5 mg Tablet, film coated Oral 25 mg Tablet, for suspension Oral 2.5 mg/1 Tablet Oral Tablet, coated Oral Injection Intramuscular 600 mg Injection Intramuscular 900 mg Injection, suspension Intramuscular 600 MG Injection, suspension Intramuscular 900 MG Suspension Intramuscular 300 mg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US5914331 Yes 1999-06-22 2018-01-02 US US6043230 Yes 2000-03-28 2018-01-25 US US9242986 Yes 2016-01-26 2030-06-08 US US5814639 Yes 1998-09-29 2017-03-29 US US6642245 Yes 2003-11-04 2021-05-04 US US6703396 Yes 2004-03-09 2021-09-09 US US5922695 Yes 1999-07-13 2018-01-25 US US5935946 Yes 1999-08-10 2018-01-25 US US5977089 Yes 1999-11-02 2018-01-25 US US8592397 No 2013-11-26 2024-01-13 US US8716264 No 2014-05-06 2024-01-13 US US7125879 Yes 2006-10-24 2025-10-21 US US6838464 No 2005-01-04 2021-02-26 US US8080551 No 2011-12-20 2023-04-11 US US8101629 No 2012-01-24 2022-08-09 US US7067522 No 2006-06-27 2019-12-20 US US7638522 No 2009-12-29 2023-04-14 US US8129385 Yes 2012-03-06 2028-04-05 US US8841310 No 2014-09-23 2025-12-09 US US9296769 Yes 2016-03-29 2033-02-15 US US7803788 No 2010-09-28 2022-02-02 US US8754065 Yes 2014-06-17 2033-02-15 US US7390791 Yes 2008-06-24 2025-10-17 US US9457036 No 2016-10-04 2024-01-13 US US9744181 No 2017-08-29 2024-01-13 US US10426780 No 2019-10-01 2031-01-24 US US10857102 No 2020-12-08 2033-01-14 US US8410103 No 2013-04-02 2026-04-28 US US10927129 No 2021-02-23 2026-04-28 US US11224597 No 2011-09-15 2031-09-15 US US11389447 No 2007-06-30 2027-06-30 US US11065198 No 2017-10-23 2037-10-23 US US12011506 No 2018-09-05 2038-09-05 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 241-243°C Sun, et al.: J. Med. Chem., 41, 4648 (1998) Kashiwada, et al.: Bioorg. Med. Chem. Lett., 11, 183 (2001) water solubility <0.1mg/ml Usach, et al. J Int AIDS Soc. 16(1): 18567. (2013) logP 4.86 Usach, et al. J Int AIDS Soc. 16(1): 18567. (2013) pKa 5.6 Usach, et al. J Int AIDS Soc. 16(1): 18567. (2013) - Predicted Properties
Property Value Source Water Solubility 0.0116 mg/mL ALOGPS logP 3.8 ALOGPS logP 5.47 Chemaxon logS -4.5 ALOGPS pKa (Strongest Acidic) 11.43 Chemaxon pKa (Strongest Basic) 4.44 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 6 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 97.42 Å2 Chemaxon Rotatable Bond Count 5 Chemaxon Refractivity 111.74 m3·mol-1 Chemaxon Polarizability 40.63 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9929 Blood Brain Barrier + 0.8571 Caco-2 permeable + 0.6609 P-glycoprotein substrate Non-substrate 0.6933 P-glycoprotein inhibitor I Non-inhibitor 0.6604 P-glycoprotein inhibitor II Non-inhibitor 0.7001 Renal organic cation transporter Non-inhibitor 0.8261 CYP450 2C9 substrate Non-substrate 0.7898 CYP450 2D6 substrate Non-substrate 0.8322 CYP450 3A4 substrate Non-substrate 0.6778 CYP450 1A2 substrate Inhibitor 0.8256 CYP450 2C9 inhibitor Non-inhibitor 0.9105 CYP450 2D6 inhibitor Non-inhibitor 0.9202 CYP450 2C19 inhibitor Non-inhibitor 0.806 CYP450 3A4 inhibitor Non-inhibitor 0.9013 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.5439 Ames test Non AMES toxic 0.6229 Carcinogenicity Non-carcinogens 0.9097 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.8139 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9027 hERG inhibition (predictor II) Non-inhibitor 0.841
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-014i-0649000000-96980e5526a79d124034 Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-014i-0009000000-86d701fd5fe683bc57af Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0006-0009000000-fa7c070ebe5898e76f1d Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-014i-0009000000-aeb728d3ab6a115d9917 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-014i-0009000000-1aac1ace211699bcbd96 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0006-0219000000-b38116130132fbe72b5d Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-014s-1940000000-2b13ad7eff3b6ae2c5b8 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 220.0854523 predictedDarkChem Lite v0.1.0 [M-H]- 219.0703523 predictedDarkChem Lite v0.1.0 [M-H]- 185.87868 predictedDeepCCS 1.0 (2019) [M+H]+ 221.2150523 predictedDarkChem Lite v0.1.0 [M+H]+ 221.4128523 predictedDarkChem Lite v0.1.0 [M+H]+ 188.23668 predictedDeepCCS 1.0 (2019) [M+Na]+ 219.4453523 predictedDarkChem Lite v0.1.0 [M+Na]+ 219.6785523 predictedDarkChem Lite v0.1.0 [M+Na]+ 194.64583 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Human immunodeficiency virus 1
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Not Available
- Specific Function
- aspartic-type endopeptidase activity
- Gene Name
- pol
- Uniprot ID
- Q72547
- Uniprot Name
- Reverse transcriptase/RNaseH
- Molecular Weight
- 65223.615 Da
References
- Garvey L, Winston A: Rilpivirine: a novel non-nucleoside reverse transcriptase inhibitor. Expert Opin Investig Drugs. 2009 Jul;18(7):1035-41. doi: 10.1517/13543780903055056. [Article]
- De Clercq E: Emerging anti-HIV drugs. Expert Opin Emerg Drugs. 2005 May;10(2):241-73. [Article]
- Australian Government: Australian Public Assessment Report for Rilpivirine [Link]
- FDA Approved Drug Products: Edurant (rilpivirine) oral tablets [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Tetrodotoxin-resistant channel that mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which sodium ions may pass in accordance with their electrochemical gradient. Plays a role in neuropathic pain mechanisms
- Specific Function
- transmembrane transporter binding
- Gene Name
- SCN10A
- Uniprot ID
- Q9Y5Y9
- Uniprot Name
- Sodium channel protein type 10 subunit alpha
- Molecular Weight
- 220623.605 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
- Not Available
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Gag-Pol polyprotein Mediates, with Gag polyprotein, the essential events in virion assembly, including binding the plasma membrane, making the protein-protein interactions necessary to create spherical particles, recruiting the viral Env proteins, and packaging the genomic RNA via direct interactions with the RNA packaging sequence (Psi). Gag-Pol polyprotein may regulate its own translation, by the binding genomic RNA in the 5'-UTR. At low concentration, the polyprotein would promote translation, whereas at high concentration, the polyprotein would encapsidate genomic RNA and then shut off translation.
- Specific Function
- aspartic-type endopeptidase activity
- Gene Name
- gag-pol
- Uniprot ID
- P03366
- Uniprot Name
- Gag-Pol polyprotein
- Molecular Weight
- 163287.51 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
- Agonist
- General Function
- Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism and secretion of potentially harmful xenobiotics, drugs and endogenous compounds. Activated by the antibiotic rifampicin and various plant metabolites, such as hyperforin, guggulipid, colupulone, and isoflavones. Response to specific ligands is species-specific. Activated by naturally occurring steroids, such as pregnenolone and progesterone. Binds to a response element in the promoters of the CYP3A4 and ABCB1/MDR1 genes
- Specific Function
- DNA-binding transcription activator activity, RNA polymerase II-specific
- Gene Name
- NR1I2
- Uniprot ID
- O75469
- Uniprot Name
- Nuclear receptor subfamily 1 group I member 2
- Molecular Weight
- 49761.245 Da
References
- Sharma D, Lau AJ, Sherman MA, Chang TK: Agonism of human pregnane X receptor by rilpivirine and etravirine: comparison with first generation non-nucleoside reverse transcriptase inhibitors. Biochem Pharmacol. 2013 Jun 1;85(11):1700-11. doi: 10.1016/j.bcp.2013.04.002. Epub 2013 Apr 9. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- SubstrateInhibitorInducer
- 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
- Weiss J, Haefeli WE: Potential of the novel antiretroviral drug rilpivirine to modulate the expression and function of drug transporters and drug-metabolising enzymes in vitro. Int J Antimicrob Agents. 2013 May;41(5):484-7. doi: 10.1016/j.ijantimicag.2013.01.004. Epub 2013 Feb 18. [Article]
- FDA Approved Drug Products: Edurant (rilpivirine) oral tablets [Link]
- Australian Government: Australian Public Assessment Report for Rilpivirine [Link]
- Rilpivirine FDA label [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- 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
- Weiss J, Haefeli WE: Potential of the novel antiretroviral drug rilpivirine to modulate the expression and function of drug transporters and drug-metabolising enzymes in vitro. Int J Antimicrob Agents. 2013 May;41(5):484-7. doi: 10.1016/j.ijantimicag.2013.01.004. Epub 2013 Feb 18. [Article]
- Aouri M, Barcelo C, Guidi M, Rotger M, Cavassini M, Hizrel C, Buclin T, Decosterd LA, Csajka C: Population Pharmacokinetics and Pharmacogenetics Analysis of Rilpivirine in HIV-1-Infected Individuals. Antimicrob Agents Chemother. 2016 Dec 27;61(1). pii: AAC.00899-16. doi: 10.1128/AAC.00899-16. Print 2017 Jan. [Article]
- Australian Government: Australian Public Assessment Report for Rilpivirine [Link]
- Actual and Predicted Pharmacokinetic Interactions Between Anticonvulsants and Antiretrovirals [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of endocannabinoids and steroids (PubMed:12865317, PubMed:21289075). 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 epoxidation of double bonds of arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:21289075). Hydroxylates steroid hormones, including testosterone at C-16 and estrogens at C-2 (PubMed:12865317, PubMed:21289075). Plays a role in the oxidative metabolism of xenobiotics, including plant lipids and drugs (PubMed:11695850, PubMed:22909231). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850)
- Specific Function
- anandamide 11,12 epoxidase activity
- Gene Name
- CYP2B6
- Uniprot ID
- P20813
- Uniprot Name
- Cytochrome P450 2B6
- Molecular Weight
- 56277.81 Da
References
- Weiss J, Haefeli WE: Potential of the novel antiretroviral drug rilpivirine to modulate the expression and function of drug transporters and drug-metabolising enzymes in vitro. Int J Antimicrob Agents. 2013 May;41(5):484-7. doi: 10.1016/j.ijantimicag.2013.01.004. Epub 2013 Feb 18. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of fatty acids, steroids and retinoids (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, 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) (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:19965576, PubMed:20972997). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:18698000, PubMed:21289075). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Catalyzes the oxidative transformations of all-trans retinol to all-trans retinal, a precursor for the active form all-trans-retinoic acid (PubMed:10681376). Also involved in the oxidative metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants
- Specific Function
- anandamide 11,12 epoxidase activity
- Gene Name
- CYP2D6
- Uniprot ID
- P10635
- Uniprot Name
- Cytochrome P450 2D6
- Molecular Weight
- 55768.94 Da
References
- Weiss J, Haefeli WE: Potential of the novel antiretroviral drug rilpivirine to modulate the expression and function of drug transporters and drug-metabolising enzymes in vitro. Int J Antimicrob Agents. 2013 May;41(5):484-7. doi: 10.1016/j.ijantimicag.2013.01.004. Epub 2013 Feb 18. [Article]
- Australian Government: Australian Public Assessment Report for Rilpivirine [Link]
- 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
- Australian Government: Australian Public Assessment Report for Rilpivirine [Link]
- 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
- Australian Government: Australian Public Assessment Report for Rilpivirine [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of fatty acids (PubMed:10553002, PubMed:18577768). 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:10553002, PubMed:18577768). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates fatty acids specifically at the omega-1 position displaying the highest catalytic activity for saturated fatty acids (PubMed:10553002, PubMed:18577768). May be involved in the oxidative metabolism of xenobiotics (Probable)
- Specific Function
- 4-nitrophenol 2-monooxygenase activity
- Gene Name
- CYP2E1
- Uniprot ID
- P05181
- Uniprot Name
- Cytochrome P450 2E1
- Molecular Weight
- 56848.42 Da
References
- Australian Government: Australian Public Assessment Report for Rilpivirine [Link]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- 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
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- ATP-dependent translocase ABCB1
- Molecular Weight
- 141477.255 Da
References
- Weiss J, Haefeli WE: Potential of the novel antiretroviral drug rilpivirine to modulate the expression and function of drug transporters and drug-metabolising enzymes in vitro. Int J Antimicrob Agents. 2013 May;41(5):484-7. doi: 10.1016/j.ijantimicag.2013.01.004. Epub 2013 Feb 18. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Broad substrate specificity ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes a wide variety of physiological compounds, dietary toxins and xenobiotics from cells (PubMed:11306452, PubMed:12958161, PubMed:19506252, PubMed:20705604, PubMed:28554189, PubMed:30405239, PubMed:31003562). Involved in porphyrin homeostasis, mediating the export of protoporphyrin IX (PPIX) from both mitochondria to cytosol and cytosol to extracellular space, it also functions in the cellular export of heme (PubMed:20705604, PubMed:23189181). Also mediates the efflux of sphingosine-1-P from cells (PubMed:20110355). Acts as a urate exporter functioning in both renal and extrarenal urate excretion (PubMed:19506252, PubMed:20368174, PubMed:22132962, PubMed:31003562, PubMed:36749388). In kidney, it also functions as a physiological exporter of the uremic toxin indoxyl sulfate (By similarity). Also involved in the excretion of steroids like estrone 3-sulfate/E1S, 3beta-sulfooxy-androst-5-en-17-one/DHEAS, and other sulfate conjugates (PubMed:12682043, PubMed:28554189, PubMed:30405239). Mediates the secretion of the riboflavin and biotin vitamins into milk (By similarity). Extrudes pheophorbide a, a phototoxic porphyrin catabolite of chlorophyll, reducing its bioavailability (By similarity). Plays an important role in the exclusion of xenobiotics from the brain (Probable). It confers to cells a resistance to multiple drugs and other xenobiotics including mitoxantrone, pheophorbide, camptothecin, methotrexate, azidothymidine, and the anthracyclines daunorubicin and doxorubicin, through the control of their efflux (PubMed:11306452, PubMed:12477054, PubMed:15670731, PubMed:18056989, PubMed:31254042). In placenta, it limits the penetration of drugs from the maternal plasma into the fetus (By similarity). May play a role in early stem cell self-renewal by blocking differentiation (By similarity)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCG2
- Uniprot ID
- Q9UNQ0
- Uniprot Name
- Broad substrate specificity ATP-binding cassette transporter ABCG2
- Molecular Weight
- 72313.47 Da
References
- Weiss J, Haefeli WE: Potential of the novel antiretroviral drug rilpivirine to modulate the expression and function of drug transporters and drug-metabolising enzymes in vitro. Int J Antimicrob Agents. 2013 May;41(5):484-7. doi: 10.1016/j.ijantimicag.2013.01.004. Epub 2013 Feb 18. [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
- Weiss J, Haefeli WE: Potential of the novel antiretroviral drug rilpivirine to modulate the expression and function of drug transporters and drug-metabolising enzymes in vitro. Int J Antimicrob Agents. 2013 May;41(5):484-7. doi: 10.1016/j.ijantimicag.2013.01.004. Epub 2013 Feb 18. [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
- Weiss J, Haefeli WE: Potential of the novel antiretroviral drug rilpivirine to modulate the expression and function of drug transporters and drug-metabolising enzymes in vitro. Int J Antimicrob Agents. 2013 May;41(5):484-7. doi: 10.1016/j.ijantimicag.2013.01.004. Epub 2013 Feb 18. [Article]
Drug created at March 14, 2013 21:23 / Updated at October 29, 2024 14:47