Explore a selection of our essential drug information below, or:
Identification
- Summary
Tenofovir alafenamide is a nucleoside analog reverse transcriptase inhibitor used for the treatment of chronic hepatitis B virus infection in adults with compensated liver disease.
- Brand Names
- Biktarvy, Descovy, Genvoya, Odefsey, Vemlidy
- Generic Name
- Tenofovir alafenamide
- DrugBank Accession Number
- DB09299
- Background
Tenofovir alafenamide is a novel tenofovir prodrug developed in order to improve renal safety when compared to the counterpart tenofovir disoproxil.1 Both of these prodrugs were first created to cover the polar phosphonic acid group on tenofovir by using a novel oxycarbonyloxymethyl linkers to improve the oral bioavailability and intestinal diffusion.8 Tenofovir alafenamide is an alanine ester form characterized for presenting low systemic levels but high intracellular concentration.2 It has been reported to produce a large antiviral efficacy at doses ten times lower than tenofovir disoproxil.6 Tenofovir alafenamide is indicated to treat chronic hepatitis B,9 treat HIV-1,11,12,13,14 and prevent HIV-1 infections.11,17
Tenofovir alafenamide was developed by Gilead Sciences Inc and granted FDA approval on 5 November 2015.10
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Tenofovir alafenamide (DB09299)
- Weight
- Average: 476.474
Monoisotopic: 476.193705056 - Chemical Formula
- C21H29N6O5P
- Synonyms
- Tenofovir alafenamide
- External IDs
- GS 7340
- GS 7340 03
- GS 734003
- GS-7340
- GS-7340-03
- GS-734003
- GS7340
- GS734003
Pharmacology
- Indication
Tenofovir alafenamide is indicated for the treatment of hepatitis B virus infection in adults and pediatric patients 12 years of age and older with compensated liver disease.18
In combination with emtricitabine and other antiretrovirals, it is indicated for the treatment of HIV-1 infection in adolescent and adult patients with a weight higher than 35 kg.11 This combination is also indicated to prevent HIV-1 infections in high-risk adolescent and adult patients, excluding patients at risk from receptive vaginal sex.11,17 When combined with antiretrovirals other than protease inhibitors that require a CYP3A inhibitor, it can be used to treat pediatric patients weighing 25-35 kg.11
In the combination product with emtricitabine and bictegravir, tenofovir alafenamide is considered a complete treatment regimen for HIV-1 infections for treatment-naive patients or patients virologically suppressed for at least three months with no history of treatment failure.12,20,19 This combination product is also used to replace the current antiretroviral regimen in those who are virologically-suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen with no known or suspected substitutions associated with resistance to bictegravir or tenofovir.21
Additionally, the combination product including elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide and the combination product including emtricitabine, rilpivirine and tenofovir alafenamide can be used in the treatment of HIV-1 infection in patients older than 12 years with no previous antiretroviral therapy history or who are virologically suppressed for at least 6 months with no history of treatment failure.13
The combination product including darunavir, cobicistat, emtricitabine, and tenofovir alafenamide is indicated for the treatment of HIV-1 infection in adults without prior antiretroviral therapy or in patients virologically suppressed for 6 months and no reported resistance to darunavir or tenofovir.14
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 Chronic hepatitis b infection •••••••••••• ••••••••••• •••••• ••••••••• ••••••••••• ••••• ••••••• •••••• Used in combination to treat Hiv-1-infection Combination Product in combination with: Emtricitabine (DB00879), Cobicistat (DB09065), Darunavir (DB01264) •••••••••••• ••••• •• •••••••••• •• •••••••••• •• •••••••••• •• •••••••••• ••••••••••••• •••••••••• ••• • ••••••• ••••••••••••••• Used in combination to treat Hiv-1-infection Combination Product in combination with: Rilpivirine (DB08864), Emtricitabine (DB00879), Elvitegravir (DB09101), Cobicistat (DB09065) •••••••••••• ••••••••••••• •••••••••• ••• • ••••••• •• ••••••• •• ••••••••• ••••••• Used in combination to treat Hiv-1-infection Combination Product in combination with: Bictegravir (DB11799), Emtricitabine (DB00879) •••••••••••• ••••••••••••• ••••••••• ••• • ••••••• •• ••••••• •• ••••••••• •••••••• ••••••••• ••••• Used in combination to treat Human immunodeficiency virus type 1 (hiv-1) infection Combination Product in combination with: Emtricitabine (DB00879), Bictegravir (DB11799) •••••••••••• •• ••••••• •• ••••••••• •••••••• •••••• •• ••••• •• ••• •••••• •••••••••••••• •••••••• ••••••••••••• •••••••••• •••••• ••• •••• •••• •• •••••• ••• ••• •••••• - Associated Therapies
- 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
Tenofovir alafenamide has been shown to be a potent inhibitor of hepatitis B viral replication.4
Tenofovir alafenamide presents a better renal tolerance when compared with the counterpart tenofovir disoproxil. This improved safety profile seems to be related to a lower plasma concentration of tenofovir.1
In clinical trials, tenofovir alafenamide was shown to present 5-fold more potent antiviral activity against HIV-1 when compared to tenofovir disoproxil.1
- Mechanism of action
Tenofovir alafenamide presents 91% lower plasma concentration with an intracellular presence of about 20-fold higher when compared to tenofovir disoproxil.2 This is due to its prolonged systemic exposure and its higher intracellular accumulation of the active metabolite tenofovir diphosphate.5
Tenofovir alafenamide accumulates more in peripheral blood mononuclear cells compared to red blood cells.5
Once activated, tenofovir acts with different mechanisms including the inhibition of viral polymerase, causing chain termination and the inhibition of viral synthesis.9 To know more about the specific mechanism of action of the active form, please visit the drug entry of tenofovir.
Target Actions Organism AReverse transcriptase/RNaseH inhibitorHuman immunodeficiency virus 1 AGag-Pol polyprotein inhibitorNReverse transcriptase inhibitorHBV NDNA polymerase inhibitorHuman herpesvirus 2 (strain 186) - Absorption
As compared to the parent molecule, tenofovir, tenofovir alafenamide presents a lipophilic group that masks the negative charge of the parent moiety which improves its oral bioavailability.1
Tenofovir alafenamide is highly stable in plasma and, after administration of this prodrug, there is a low concentration of tenofovir in plasma. After oral administration, tenofovir alafenamide is rapidly absorbed by the gut. When a single dose is administered, a peak concentration of 16 ng/ml of the parent compound, corresponding to about 73% of the dose, is observed after 2 hours with an AUC of 270 ng*h/mL.1,5 Once inside the body, tenofovir alafenamide enters hepatocytes by passive diffusion regulated by the organic anion transporters 1B1 and 1B3 for its activation.4
Administration of tenofovir alafenamide concomitantly with a high-fat meal results in an increase of about 65% in its internal exposure.15
- Volume of distribution
In clinical trials, the reported volume of distribution of tenofovir alafenamide was higher than 100 L.7
- Protein binding
Tenofovir alafenamide is reported to bind to plasma proteins and ex vivo studies have registered that approximately 80% of the administered dose of this drug is presented in a bound state.3
- Metabolism
To be activated, tenofovir alafenamide is required to be hydrolyzed to the parent compound tenofovir by the activity of cathepsin A or carboxylesterase 1. Tenofovir alafenamide presents significant plasma stability and hence, its activation is performed inside the target cells.1
After activation, tenofovir is further processed and after 1-2 days, it is detected in plasma almost completely transformed to uric acid.1
Hover over products below to view reaction partners
- Route of elimination
Tenofovir alafenamide has been registered to present a bile elimination that corresponds to 47% of the administered dose and a renal elimination the represents about 36%. From the recovered dose in urine, about 75% is represented as unchanged tenofovir followed by uric acid and a small dose of tenofovir alafenamide. On the other hand, in feces, 99% of the recovered dose corresponds to tenofovir.1
- Half-life
The reported half-life for tenofovir alafenamide is of 0.51 hours.3
- Clearance
The reported clearance rate of tenofovir alafenamide is 117 L/h. In patients with severe renal impairment, this value can be decreased by 50%, reporting a rate of 61.7 L/h.16
- 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 LD50 of tenofovir alafenamide has not been reported. In cases of overdose, continuous monitoring of vital signs is required as the adverse effects in high doses has not been evaluated. However, in case of overdose, tenofovir is efficiently removed by hemodialysis with an extraction coefficient of 54%.15
Carcinogenic reports have only been performed with tenofovir disoproxil and it is important to consider that tenofovir alafenamide does not present a high systemic exposure. However, long-term exposure with 10-fold dosages of tenofovir disoproxil was reported to produce liver adenomas in females. Tenofovir alafenamide was not reported to present mutagenic potential and it did not present effects on fertility.15
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir The serum concentration of Tenofovir alafenamide can be increased when it is combined with Abacavir. Abametapir The serum concentration of Tenofovir alafenamide can be increased when it is combined with Abametapir. Abatacept The metabolism of Tenofovir alafenamide can be increased when combined with Abatacept. Abemaciclib The serum concentration of Tenofovir alafenamide can be increased when it is combined with Abemaciclib. Abrocitinib The serum concentration of Tenofovir alafenamide can be increased when it is combined with Abrocitinib. - Food Interactions
- Avoid St. John's Wort. St. John's Wort can cause drug interaction and decrease the serum concentration of tenofovir alafenamide.
- Take at the same time every day.
- Take with or without food. Recommendations vary from product to product - consult individual product monographs for additional information.
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 Tenofovir alafenamide fumarate FWF6Q91TZO 1392275-56-7 SVUJNSGGPUCLQZ-LVWWUONPSA-N - Active Moieties
Name Kind UNII CAS InChI Key Tenofovir prodrug W4HFE001U5 147127-20-6 SGOIRFVFHAKUTI-ZCFIWIBFSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Vemlidy Tablet, film coated 25 mg Oral Gilead Sciences Ireland Uc 2020-12-16 Not applicable EU 
Vemlidy Tablet 25 mg Oral Gilead Sciences 2017-06-20 Not applicable Canada 
Vemlidy Tablet, film coated 25 mg Oral Gilead Sciences Ireland Uc 2020-12-16 Not applicable EU Vemlidy Tablet 25 mg/1 Oral Gilead Sciences, Inc. 2016-11-10 Not applicable US 
- Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Biktarvy Tenofovir alafenamide fumarate (25 mg) + Bictegravir sodium (50 mg) + Emtricitabine (200 mg) Tablet, film coated Oral Gilead Sciences Ireland Uc 2021-06-01 Not applicable EU Biktarvy Tenofovir alafenamide fumarate (25 mg/1) + Bictegravir sodium (50 mg/1) + Emtricitabine (200 mg/1) Tablet Oral Gilead Sciences, Inc. 2018-02-07 Not applicable US Biktarvy Tenofovir alafenamide fumarate (25 mg/1) + Bictegravir sodium (50 mg/1) + Emtricitabine (200 mg/1) Tablet Oral A-S Medication Solutions 2018-02-07 Not applicable US BIKTARVY Tenofovir alafenamide (25 MG) + Bictegravir (50 MG) + Emtricitabine (200 MG) Tablet, coated Oral บริษัท ดีซีเอช ออริกา (ประเทศไทย) จำกัด 2020-01-02 Not applicable Thailand 
Biktarvy Tenofovir alafenamide fumarate (25 mg/1) + Bictegravir sodium (50 mg/1) + Emtricitabine (200 mg/1) Tablet Oral REMEDYREPACK INC. 2021-04-28 Not applicable 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
- J05AF — Nucleoside and nucleotide reverse transcriptase inhibitors
- 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
- Amino Acids
- Amino Acids, Peptides, and Proteins
- Antiinfectives for Systemic Use
- Antiviral Agents
- Antivirals for Systemic Use
- Antivirals used in combination for the treatment of HIV infections
- BCRP/ABCG2 Substrates
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A4 Substrates (strength unknown)
- Cytochrome P-450 Substrates
- Direct Acting Antivirals
- Hepatitis B Virus Nucleoside Analog Reverse Transcriptase Inhibitor
- Heterocyclic Compounds, Fused-Ring
- Human Immunodeficiency Virus Nucleoside Analog Reverse Transcriptase Inhibitor
- Nephrotoxic agents
- Nucleoside and Nucleotide Reverse Transcriptase Inhibitors
- OAT1/SLC22A6 Substrates
- OAT3/SLC22A8 Substrates
- OATP1B1/SLCO1B1 Substrates
- OATP1B3 substrates
- Organophosphonates
- Organophosphorus Compounds
- P-glycoprotein substrates
- Purines
- Tenofovir and prodrugs
- Vitamin B Complex
- Vitamins
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as alpha amino acid esters. These are ester derivatives of alpha amino acids.
- Kingdom
- Organic compounds
- Super Class
- Organic acids and derivatives
- Class
- Carboxylic acids and derivatives
- Sub Class
- Amino acids, peptides, and analogues
- Direct Parent
- Alpha amino acid esters
- Alternative Parents
- Alanine and derivatives / 6-aminopurines / Phenoxy compounds / Aminopyrimidines and derivatives / Phosphonic amide esters / Phosphonic acid esters / N-substituted imidazoles / Imidolactams / Heteroaromatic compounds / Carboxylic acid esters show 8 more
- Substituents
- 6-aminopurine / Alanine or derivatives / Alpha-amino acid ester / Amine / Aminopyrimidine / Aromatic heteropolycyclic compound / Azacycle / Azole / Benzenoid / Carbonyl group show 24 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Herpes simplex virus
- Hepatitis B virus
- HIV-1
Chemical Identifiers
- UNII
- EL9943AG5J
- CAS number
- 379270-37-8
- InChI Key
- LDEKQSIMHVQZJK-CAQYMETFSA-N
- InChI
- InChI=1S/C21H29N6O5P/c1-14(2)31-21(28)16(4)26-33(29,32-17-8-6-5-7-9-17)13-30-15(3)10-27-12-25-18-19(22)23-11-24-20(18)27/h5-9,11-12,14-16H,10,13H2,1-4H3,(H,26,29)(H2,22,23,24)/t15-,16+,33+/m1/s1
- IUPAC Name
- propan-2-yl (2S)-2-{[(S)-({[(2R)-1-(6-amino-9H-purin-9-yl)propan-2-yl]oxy}methyl)(phenoxy)phosphoryl]amino}propanoate
- SMILES
- CC(C)OC(=O)[C@H](C)N[P@](=O)(CO[C@H](C)CN1C=NC2=C(N)N=CN=C12)OC1=CC=CC=C1
References
- General References
- Aloy B, Tazi I, Bagnis CI, Gauthier M, Janus N, Launay-Vacher V, Deray G, Tourret J: Is Tenofovir Alafenamide Safer than Tenofovir Disoproxil Fumarate for the Kidneys? AIDS Rev. 2016 Oct-Dec;18(4):184-192. [Article]
- Grant PM, Cotter AG: Tenofovir and bone health. Curr Opin HIV AIDS. 2016 May;11(3):326-32. doi: 10.1097/COH.0000000000000248. [Article]
- Deeks ED: Bictegravir/Emtricitabine/Tenofovir Alafenamide: A Review in HIV-1 Infection. Drugs. 2018 Nov;78(17):1817-1828. doi: 10.1007/s40265-018-1010-7. [Article]
- Ogawa E, Furusyo N, Nguyen MH: Tenofovir alafenamide in the treatment of chronic hepatitis B: design, development, and place in therapy. Drug Des Devel Ther. 2017 Nov 6;11:3197-3204. doi: 10.2147/DDDT.S126742. eCollection 2017. [Article]
- Ray AS, Fordyce MW, Hitchcock MJ: Tenofovir alafenamide: A novel prodrug of tenofovir for the treatment of Human Immunodeficiency Virus. Antiviral Res. 2016 Jan;125:63-70. doi: 10.1016/j.antiviral.2015.11.009. Epub 2015 Nov 27. [Article]
- Antela A, Aguiar C, Compston J, Hendry BM, Boffito M, Mallon P, Pourcher-Martinez V, Di Perri G: The role of tenofovir alafenamide in future HIV management. HIV Med. 2016 May;17 Suppl 2:4-16. doi: 10.1111/hiv.12401. [Article]
- Markowitz M, Zolopa A, Squires K, Ruane P, Coakley D, Kearney B, Zhong L, Wulfsohn M, Miller MD, Lee WA: Phase I/II study of the pharmacokinetics, safety and antiretroviral activity of tenofovir alafenamide, a new prodrug of the HIV reverse transcriptase inhibitor tenofovir, in HIV-infected adults. J Antimicrob Chemother. 2014 May;69(5):1362-9. doi: 10.1093/jac/dkt532. Epub 2014 Feb 6. [Article]
- Taylor JB, Triggle DJ. (2007). Comprehensive Medicinal Chemistry II. Elsevier.
- Pubmed books [Link]
- FDA approvals [Link]
- FDA Approved Drug Products: Descovy (Emtricitabine and Tenofovir Alafenamide) Oral Tablets [Link]
- FDA Approved Drug Products: Bictegravir, Emtricitabine, and Tenofovir Alafenamide Oral Tablets [Link]
- FDA Approved Drug Products: Elvitegravir, Cobicistat, Emtricitabine, and Tenofovir Alafenamide Oral Tablets [Link]
- FDA Approved Drug Products: Darunavir, Cobicistat, Emtricitabine, and Tenofovir Alafenamide Oral Tablets [Link]
- Health Canada Approved Drug Products: Tenofovir Alafenamide Oral Tablets [Link]
- European Medicines Agency Assessment Report: Tenofovir Alafenamide [Link]
- FDA Press Announcements: FDA approves second drug to prevent HIV infection as part of ongoing efforts to end the HIV epidemic [Link]
- FDA Approved Drug Products: VEMLIDY (tenofovir alafenamide) tablets, for oral use (October 2022) [Link]
- EMA Approved Drug Products: Biktarvy (bictegravir, emtricitabine, tenofovir alafenamide) Oral Tablets [Link]
- FDA Approved Drug Products: BIKTARVY (bictegravir, emtricitabine, and tenofovir alafenamide) tablets, for oral use (October 2021) [Link]
- FDA Approved Drug Products: BIKTARVY (bictegravir, emtricitabine, and tenofovir alafenamide) tablets, for oral use (February 2024) [Link]
- External Links
- KEGG Drug
- D10428
- PubChem Compound
- 9574768
- PubChem Substance
- 310265191
- ChemSpider
- 7849225
- 1721603
- ChEBI
- 90926
- ChEMBL
- CHEMBL2107825
- ZINC
- ZINC000100055899
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Tenofovir_alafenamide
- FDA label
- Download (1.08 MB)
- MSDS
- Download (254 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 Antiviral Treatment / Chronic Hepatitis B Infection / Fatty Liver Disease 1 somestatus stop reason just information to hide Not Available Active Not Recruiting Not Available Chronic Hepatitis B Infection 2 somestatus stop reason just information to hide Not Available Active Not Recruiting Not Available HIV, Prevention 1 somestatus stop reason just information to hide Not Available Active Not Recruiting Not Available Human Immunodeficiency Virus (HIV) Infections 1 somestatus stop reason just information to hide Not Available Active Not Recruiting Not Available Human Immunodeficiency Virus Type 1 (HIV-1) Infection 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet, coated Oral Tablet, film coated Oral 150 mg Tablet, film coated Oral 28043 MG Tablet, coated Oral 25 mg Tablet, film coated Oral Tablet Oral Tablet Oral 800.000 mg Tablet, film coated Oral Tablet, film coated Oral 28.05 MG Tablet Oral 25 mg Tablet Oral 25 mg/1 Tablet, film coated Oral 28.04 MG Tablet, film coated Oral 25.0 mg Tablet, film coated Oral 25 mg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US7800788 No 2010-09-21 2022-02-02 US US5914331 Yes 1999-06-22 2018-01-02 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 US7470506 Yes 2008-12-30 2019-12-23 US US8597876 Yes 2013-12-03 2019-12-23 US US7700645 Yes 2010-04-20 2027-06-26 US US8518987 Yes 2013-08-27 2024-08-16 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 US8148374 Yes 2012-04-03 2030-03-03 US US7635704 Yes 2009-12-22 2027-04-26 US US7176220 Yes 2007-02-13 2027-02-27 US US8981103 Yes 2015-03-17 2027-04-26 US US8633219 Yes 2014-01-21 2030-10-24 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 US9891239 Yes 2018-02-13 2030-03-03 US US9889115 Yes 2018-02-13 2019-12-23 US US9216996 No 2015-12-22 2033-12-19 US US9708342 No 2017-07-18 2035-06-19 US US9732092 No 2017-08-15 2033-12-19 US US10039718 Yes 2018-08-07 2033-04-06 US US10385067 No 2019-08-20 2035-06-19 US US10548846 No 2020-02-04 2036-11-08 US US10786515 No 2020-09-29 2038-07-19 US US10786518 No 2020-09-29 2038-07-19 US US11744802 No 2016-11-08 2036-11-08 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 104-107 ºC 'MSDS' boiling point (°C) 640 ºC at 760 mmHg 'MSDS' water solubility 4.86 mg/ml at 20 ºC Product monograph. Gilead Sciences Canada logP 1.6 Product monograph. Gilead Sciences Canada pKa 3.96 Product monograph. Gilead Sciences Canada - Predicted Properties
Property Value Source Water Solubility 0.236 mg/mL ALOGPS logP 1.49 ALOGPS logP 1.88 Chemaxon logS -3.3 ALOGPS pKa (Strongest Acidic) 11.36 Chemaxon pKa (Strongest Basic) 5.12 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 7 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 143.48 Å2 Chemaxon Rotatable Bond Count 12 Chemaxon Refractivity 122.74 m3·mol-1 Chemaxon Polarizability 47.88 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0007-9103000000-737254a45b827a74dbc3 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-004i-2114900000-106ce5efc9eca6bf7694 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-006y-9003100000-eb4bc3fad2c599361183 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0079-9522300000-493d24f75bb0677d7c5b Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-000l-9812100000-3facd0a35b7cdf8f91a0 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-000x-8972100000-8a40cff04deb28c73ec1 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]- 200.68626 predictedDeepCCS 1.0 (2019) [M+H]+ 203.08183 predictedDeepCCS 1.0 (2019) [M+Na]+ 208.99437 predictedDeepCCS 1.0 (2019)
Targets
Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
- Kind
- Protein
- Organism
- 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
- McConville C, Boyd P, Major I: Efficacy of Tenofovir 1% Vaginal Gel in Reducing the Risk of HIV-1 and HSV-2 Infection. Clin Med Insights Womens Health. 2014 Feb 13;7:1-8. doi: 10.4137/CMWH.S10353. eCollection 2014. [Article]
- Ray AS, Fordyce MW, Hitchcock MJ: Tenofovir alafenamide: A novel prodrug of tenofovir for the treatment of Human Immunodeficiency Virus. Antiviral Res. 2016 Jan;125:63-70. doi: 10.1016/j.antiviral.2015.11.009. Epub 2015 Nov 27. [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
- HBV
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Not Available
- Specific Function
- RNA-directed DNA polymerase activity
- Gene Name
- rt
- Uniprot ID
- Q3MS49
- Uniprot Name
- Reverse transcriptase
- Molecular Weight
- 4735.565 Da
References
- McConville C, Boyd P, Major I: Efficacy of Tenofovir 1% Vaginal Gel in Reducing the Risk of HIV-1 and HSV-2 Infection. Clin Med Insights Womens Health. 2014 Feb 13;7:1-8. doi: 10.4137/CMWH.S10353. eCollection 2014. [Article]
- Ray AS, Fordyce MW, Hitchcock MJ: Tenofovir alafenamide: A novel prodrug of tenofovir for the treatment of Human Immunodeficiency Virus. Antiviral Res. 2016 Jan;125:63-70. doi: 10.1016/j.antiviral.2015.11.009. Epub 2015 Nov 27. [Article]
- Kind
- Protein
- Organism
- Human herpesvirus 2 (strain 186)
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Replicates viral genomic DNA. The replication complex is composed of six viral proteins: the DNA polymerase, processivity factor, primase, primase-associated factor, helicase, and ssDNA-binding protein. Additionally, the polymerase contains an intrinsic ribonuclease H (RNase H) activity that specifically degrades RNA/DNA heteroduplexes or duplex DNA substrates in the 5' to 3' direction. Therefore, it can catalyze the excision of the RNA primers that initiate the synthesis of Okazaki fragments at a replication fork during viral DNA replication.
- Specific Function
- 3'-5'-DNA exonuclease activity
- Gene Name
- Not Available
- Uniprot ID
- I6TLU5
- Uniprot Name
- DNA polymerase
- Molecular Weight
- 137296.405 Da
References
- McConville C, Boyd P, Major I: Efficacy of Tenofovir 1% Vaginal Gel in Reducing the Risk of HIV-1 and HSV-2 Infection. Clin Med Insights Womens Health. 2014 Feb 13;7:1-8. doi: 10.4137/CMWH.S10353. eCollection 2014. [Article]
- Ray AS, Fordyce MW, Hitchcock MJ: Tenofovir alafenamide: A novel prodrug of tenofovir for the treatment of Human Immunodeficiency Virus. Antiviral Res. 2016 Jan;125:63-70. doi: 10.1016/j.antiviral.2015.11.009. Epub 2015 Nov 27. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Protective protein appears to be essential for both the activity of beta-galactosidase and neuraminidase, it associates with these enzymes and exerts a protective function necessary for their stability and activity. This protein is also a carboxypeptidase and can deamidate tachykinins.
- Specific Function
- carboxypeptidase activity
- Gene Name
- CTSA
- Uniprot ID
- P10619
- Uniprot Name
- Lysosomal protective protein
- Molecular Weight
- 54465.655 Da
References
- Aloy B, Tazi I, Bagnis CI, Gauthier M, Janus N, Launay-Vacher V, Deray G, Tourret J: Is Tenofovir Alafenamide Safer than Tenofovir Disoproxil Fumarate for the Kidneys? AIDS Rev. 2016 Oct-Dec;18(4):184-192. [Article]
- Deeks ED: Bictegravir/Emtricitabine/Tenofovir Alafenamide: A Review in HIV-1 Infection. Drugs. 2018 Nov;78(17):1817-1828. doi: 10.1007/s40265-018-1010-7. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs (PubMed:18762277, PubMed:7980644, PubMed:9169443, PubMed:9490062). Hydrolyzes aromatic and aliphatic esters, but has no catalytic activity toward amides or a fatty acyl-CoA ester (PubMed:18762277, PubMed:7980644, PubMed:9169443, PubMed:9490062). Hydrolyzes the methyl ester group of cocaine to form benzoylecgonine (PubMed:7980644). Catalyzes the transesterification of cocaine to form cocaethylene (PubMed:7980644). Displays fatty acid ethyl ester synthase activity, catalyzing the ethyl esterification of oleic acid to ethyloleate (PubMed:7980644). Converts monoacylglycerides to free fatty acids and glycerol. Hydrolyzes of 2-arachidonoylglycerol and prostaglandins (PubMed:21049984). Hydrolyzes cellular cholesteryl esters to free cholesterols and promotes reverse cholesterol transport (RCT) by facilitating both the initial and final steps in the process (PubMed:11015575, PubMed:16024911, PubMed:16971496, PubMed:18762277). First of all, allows free cholesterol efflux from macrophages to extracellular cholesterol acceptors and secondly, releases free cholesterol from lipoprotein-delivered cholesteryl esters in the liver for bile acid synthesis or direct secretion into the bile (PubMed:16971496, PubMed:18599737, PubMed:18762277).
- Specific Function
- carboxylesterase activity
- Gene Name
- CES1
- Uniprot ID
- P23141
- Uniprot Name
- Liver carboxylesterase 1
- Molecular Weight
- 62520.62 Da
References
- Aloy B, Tazi I, Bagnis CI, Gauthier M, Janus N, Launay-Vacher V, Deray G, Tourret J: Is Tenofovir Alafenamide Safer than Tenofovir Disoproxil Fumarate for the Kidneys? AIDS Rev. 2016 Oct-Dec;18(4):184-192. [Article]
- Deeks ED: Bictegravir/Emtricitabine/Tenofovir Alafenamide: A Review in HIV-1 Infection. Drugs. 2018 Nov;78(17):1817-1828. doi: 10.1007/s40265-018-1010-7. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- 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
- FDA Approved Drug Products: Bictegravir, Emtricitabine, and Tenofovir Alafenamide Oral Tablets [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Catalyzes the reversible transfer of the terminal phosphate group between ATP and AMP (PubMed:2542324). Exhibits nucleoside diphosphate kinase activity, catalyzing the production of ATP, CTP, GTP, UTP, dATP, dCTP, dGTP and dTTP from the corresponding diphosphate substrates with either ATP or GTP as phosphate donor (PubMed:23416111). Also catalyzes at a very low rate the synthesis of thiamine triphosphate (ThTP) from thiamine diphosphate (ThDP) and ADP (By similarity).
- Specific Function
- adenylate kinase activity
- Gene Name
- AK1
- Uniprot ID
- P00568
- Uniprot Name
- Adenylate kinase isoenzyme 1
- Molecular Weight
- 21634.725 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Catalyzes the reversible transfer of the terminal phosphate group between ATP and AMP. Plays an important role in cellular energy homeostasis and in adenine nucleotide metabolism. Adenylate kinase activity is critical for regulation of the phosphate utilization and the AMP de novo biosynthesis pathways. Plays a key role in hematopoiesis.
- Specific Function
- adenylate kinase activity
- Gene Name
- AK2
- Uniprot ID
- P54819
- Uniprot Name
- Adenylate kinase 2, mitochondrial
- Molecular Weight
- 26477.44 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Major role in the synthesis of nucleoside triphosphates other than ATP. The ATP gamma phosphate is transferred to the NDP beta phosphate via a ping-pong mechanism, using a phosphorylated active-site intermediate. Possesses nucleoside-diphosphate kinase, serine/threonine-specific protein kinase, geranyl and farnesyl pyrophosphate kinase, histidine protein kinase and 3'-5' exonuclease activities. Involved in cell proliferation, differentiation and development, signal transduction, G protein-coupled receptor endocytosis, and gene expression. Required for neural development including neural patterning and cell fate determination. During GZMA-mediated cell death, works in concert with TREX1. NME1 nicks one strand of DNA and TREX1 removes bases from the free 3' end to enhance DNA damage and prevent DNA end reannealing and rapid repair.
- Specific Function
- 3'-5' exonuclease activity
- Gene Name
- NME1
- Uniprot ID
- P15531
- Uniprot Name
- Nucleoside diphosphate kinase A
- Molecular Weight
- 17148.635 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Major role in the synthesis of nucleoside triphosphates other than ATP. The ATP gamma phosphate is transferred to the NDP beta phosphate via a ping-pong mechanism, using a phosphorylated active-site intermediate (By similarity). Negatively regulates Rho activity by interacting with AKAP13/LBC (PubMed:15249197). Acts as a transcriptional activator of the MYC gene; binds DNA non-specifically (PubMed:19435876, PubMed:8392752). Binds to both single-stranded guanine- and cytosine-rich strands within the nuclease hypersensitive element (NHE) III(1) region of the MYC gene promoter. Does not bind to duplex NHE III(1) (PubMed:19435876). Has G-quadruplex (G4) DNA-binding activity, which is independent of its nucleotide-binding and kinase activity. Binds both folded and unfolded G4 with similar low nanomolar affinities. Stabilizes folded G4s regardless of whether they are prefolded or not (PubMed:25679041). Exhibits histidine protein kinase activity (PubMed:20946858).
- Specific Function
- ATP binding
- Gene Name
- NME2
- Uniprot ID
- P22392
- Uniprot Name
- Nucleoside diphosphate kinase B
- Molecular Weight
- 17297.935 Da
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
- Deeks ED: Bictegravir/Emtricitabine/Tenofovir Alafenamide: A Review in HIV-1 Infection. Drugs. 2018 Nov;78(17):1817-1828. doi: 10.1007/s40265-018-1010-7. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218).
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- ATP-dependent translocase ABCB1
- Molecular Weight
- 141477.255 Da
References
- Soriano V, Labarga P, Fernandez-Montero JV, Mendoza C, Benitez-Gutierrez L, Pena JM, Barreiro P: Drug interactions in HIV-infected patients treated for hepatitis C. Expert Opin Drug Metab Toxicol. 2017 Aug;13(8):807-816. doi: 10.1080/17425255.2017.1351942. Epub 2017 Jul 13. [Article]
- Begley R, Das M, Zhong L, Ling J, Kearney BP, Custodio JM: Pharmacokinetics of Tenofovir Alafenamide When Coadministered With Other HIV Antiretrovirals. J Acquir Immune Defic Syndr. 2018 Aug 1;78(4):465-472. doi: 10.1097/QAI.0000000000001699. [Article]
- Custodio JM, Fordyce M, Garner W, Vimal M, Ling KH, Kearney BP, Ramanathan S: Pharmacokinetics and Safety of Tenofovir Alafenamide in HIV-Uninfected Subjects with Severe Renal Impairment. Antimicrob Agents Chemother. 2016 Aug 22;60(9):5135-40. doi: 10.1128/AAC.00005-16. Print 2016 Sep. [Article]
- Murakami E, Wang T, Park Y, Hao J, Lepist EI, Babusis D, Ray AS: Implications of efficient hepatic delivery by tenofovir alafenamide (GS-7340) for hepatitis B virus therapy. Antimicrob Agents Chemother. 2015;59(6):3563-9. doi: 10.1128/AAC.00128-15. Epub 2015 Apr 13. [Article]
- Aloy B, Tazi I, Bagnis CI, Gauthier M, Janus N, Launay-Vacher V, Deray G, Tourret J: Is Tenofovir Alafenamide Safer than Tenofovir Disoproxil Fumarate for the Kidneys? AIDS Rev. 2016 Oct-Dec;18(4):184-192. [Article]
- HIV insite, UCSF: Tenofovir Alafenamide [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds and xenobiotics from cells. Transports a range of endogenous molecules that have a key role in cellular communication and signaling, including cyclic nucleotides such as cyclic AMP (cAMP) and cyclic GMP (cGMP), bile acids, steroid conjugates, urate, and prostaglandins (PubMed:11856762, PubMed:12523936, PubMed:12835412, PubMed:12883481, PubMed:15364914, PubMed:15454390, PubMed:16282361, PubMed:17959747, PubMed:18300232, PubMed:26721430). Mediates the ATP-dependent efflux of glutathione conjugates such as leukotriene C4 (LTC4) and leukotriene B4 (LTB4) too. The presence of GSH is necessary for the ATP-dependent transport of LTB4, whereas GSH is not required for the transport of LTC4 (PubMed:17959747). Mediates the cotransport of bile acids with reduced glutathione (GSH) (PubMed:12523936, PubMed:12883481, PubMed:16282361). Transports a wide range of drugs and their metabolites, including anticancer, antiviral and antibiotics molecules (PubMed:11856762, PubMed:12105214, PubMed:15454390, PubMed:17344354, PubMed:18300232). Confers resistance to anticancer agents such as methotrexate (PubMed:11106685).
- Specific Function
- 15-hydroxyprostaglandin dehydrogenase (NAD+) activity
- Gene Name
- ABCC4
- Uniprot ID
- O15439
- Uniprot Name
- ATP-binding cassette sub-family C member 4
- Molecular Weight
- 149525.33 Da
References
- Aloy B, Tazi I, Bagnis CI, Gauthier M, Janus N, Launay-Vacher V, Deray G, Tourret J: Is Tenofovir Alafenamide Safer than Tenofovir Disoproxil Fumarate for the Kidneys? AIDS Rev. 2016 Oct-Dec;18(4):184-192. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Secondary active transporter that functions as a Na(+)-independent organic anion (OA)/dicarboxylate antiporter where the uptake of one molecule of OA into the cell is coupled with an efflux of one molecule of intracellular dicarboxylate such as 2-oxoglutarate or glutarate (PubMed:11669456, PubMed:11907186, PubMed:14675047, PubMed:22108572, PubMed:23832370, PubMed:28534121, PubMed:9950961). Mediates the uptake of OA across the basolateral side of proximal tubule epithelial cells, thereby contributing to the renal elimination of endogenous OA from the systemic circulation into the urine (PubMed:9887087). 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). Transports prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) and may contribute to their renal excretion (PubMed:11907186). Also mediates the uptake of cyclic nucleotides such as cAMP and cGMP (PubMed:26377792). Involved in the transport of neuroactive tryptophan metabolites kynurenate (KYNA) and xanthurenate (XA) and may contribute to their secretion from the brain (PubMed:22108572, PubMed:23832370). May transport glutamate (PubMed:26377792). Also involved in the disposition of uremic toxins and potentially toxic xenobiotics by the renal organic anion secretory pathway, helping reduce their undesired toxicological effects on the body (PubMed:11669456, PubMed:14675047). Uremic toxins include the indoxyl sulfate (IS), hippurate/N-benzoylglycine (HA), indole acetate (IA), 3-carboxy-4- methyl-5-propyl-2-furanpropionate (CMPF) and urate (PubMed:14675047, PubMed:26377792). Xenobiotics include the mycotoxin ochratoxin (OTA) (PubMed:11669456). May also contribute to the transport of organic compounds in testes across the blood-testis-barrier (PubMed:35307651).
- Specific Function
- alpha-ketoglutarate transmembrane transporter activity
- Gene Name
- SLC22A6
- Uniprot ID
- Q4U2R8
- Uniprot Name
- Solute carrier family 22 member 6
- Molecular Weight
- 61815.78 Da
References
- Aloy B, Tazi I, Bagnis CI, Gauthier M, Janus N, Launay-Vacher V, Deray G, Tourret J: Is Tenofovir Alafenamide Safer than Tenofovir Disoproxil Fumarate for the Kidneys? AIDS Rev. 2016 Oct-Dec;18(4):184-192. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- 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
- Aloy B, Tazi I, Bagnis CI, Gauthier M, Janus N, Launay-Vacher V, Deray G, Tourret J: Is Tenofovir Alafenamide Safer than Tenofovir Disoproxil Fumarate for the Kidneys? AIDS Rev. 2016 Oct-Dec;18(4):184-192. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Broad substrate specificity ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes a wide variety of physiological compounds, dietary toxins and xenobiotics from cells (PubMed:11306452, PubMed:12958161, PubMed:19506252, PubMed:20705604, PubMed:28554189, PubMed:30405239, PubMed:31003562). Involved in porphyrin homeostasis, mediating the export of protoporphyrin IX (PPIX) from both mitochondria to cytosol and cytosol to extracellular space, it also functions in the cellular export of heme (PubMed:20705604, PubMed:23189181). Also mediates the efflux of sphingosine-1-P from cells (PubMed:20110355). Acts as a urate exporter functioning in both renal and extrarenal urate excretion (PubMed:19506252, PubMed:20368174, PubMed:22132962, PubMed:31003562, PubMed:36749388). In kidney, it also functions as a physiological exporter of the uremic toxin indoxyl sulfate (By similarity). Also involved in the excretion of steroids like estrone 3-sulfate/E1S, 3beta-sulfooxy-androst-5-en-17-one/DHEAS, and other sulfate conjugates (PubMed:12682043, PubMed:28554189, PubMed:30405239). Mediates the secretion of the riboflavin and biotin vitamins into milk (By similarity). Extrudes pheophorbide a, a phototoxic porphyrin catabolite of chlorophyll, reducing its bioavailability (By similarity). Plays an important role in the exclusion of xenobiotics from the brain (Probable). It confers to cells a resistance to multiple drugs and other xenobiotics including mitoxantrone, pheophorbide, camptothecin, methotrexate, azidothymidine, and the anthracyclines daunorubicin and doxorubicin, through the control of their efflux (PubMed:11306452, PubMed:12477054, PubMed:15670731, PubMed:18056989, PubMed:31254042). In placenta, it limits the penetration of drugs from the maternal plasma into the fetus (By similarity). May play a role in early stem cell self-renewal by blocking differentiation (By similarity).
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCG2
- Uniprot ID
- Q9UNQ0
- Uniprot Name
- Broad substrate specificity ATP-binding cassette transporter ABCG2
- Molecular Weight
- 72313.47 Da
References
- Deeks ED: Bictegravir/Emtricitabine/Tenofovir Alafenamide: A Review in HIV-1 Infection. Drugs. 2018 Nov;78(17):1817-1828. doi: 10.1007/s40265-018-1010-7. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- 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
- Ogawa E, Furusyo N, Nguyen MH: Tenofovir alafenamide in the treatment of chronic hepatitis B: design, development, and place in therapy. Drug Des Devel Ther. 2017 Nov 6;11:3197-3204. doi: 10.2147/DDDT.S126742. eCollection 2017. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- 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
- Ogawa E, Furusyo N, Nguyen MH: Tenofovir alafenamide in the treatment of chronic hepatitis B: design, development, and place in therapy. Drug Des Devel Ther. 2017 Nov 6;11:3197-3204. doi: 10.2147/DDDT.S126742. eCollection 2017. [Article]
Drug created at November 08, 2015 21:16 / Updated at August 26, 2024 19:23