Identification

Name
Tenofovir alafenamide
Accession Number
DB09299
Description

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
Thumb
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 chronic hepatitis B in adult patients with compensated liver disease.9

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 as a complete regimen for the treatment of HIV-1 infection in treatment-naive patients or in patients virologically suppressed for at least 3 months with no history of treatment failure.12

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

Associated Conditions
Contraindications & Blackbox Warnings
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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.

TargetActionsOrganism
AReverse transcriptase/RNaseH
inhibitor
Human immunodeficiency virus 1
NReverse transcriptase
inhibitor
HBV
NDNA polymerase
inhibitor
Human 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
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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

Affected organisms
  • Herpes simplex virus
  • Hepatitis B virus
  • HIV-1
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.
DrugInteraction
AbacavirTenofovir alafenamide may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbametapirThe serum concentration of Tenofovir alafenamide can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Tenofovir alafenamide can be increased when combined with Abatacept.
AbemaciclibAbemaciclib may decrease the excretion rate of Tenofovir alafenamide which could result in a higher serum level.
AbirateroneThe metabolism of Abiraterone can be decreased when combined with Tenofovir alafenamide.
AcalabrutinibThe metabolism of Tenofovir alafenamide can be decreased when combined with Acalabrutinib.
AcarboseTenofovir alafenamide may decrease the excretion rate of Acarbose which could result in a higher serum level.
AceclofenacAceclofenac may increase the nephrotoxic activities of Tenofovir alafenamide.
AcemetacinAcemetacin may increase the nephrotoxic activities of Tenofovir alafenamide.
AcenocoumarolThe metabolism of Acenocoumarol can be decreased when combined with Tenofovir alafenamide.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
  • 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

Product Ingredients
IngredientUNIICASInChI Key
Tenofovir alafenamide fumarateFWF6Q91TZO1392275-56-7SVUJNSGGPUCLQZ-FQQAACOVSA-N
Active Moieties
NameKindUNIICASInChI Key
TenofovirprodrugW4HFE001U5147127-20-6SGOIRFVFHAKUTI-ZCFIWIBFSA-N
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
OdefseyTablet, film coatedOralGilead Sciences Ireland Uc2016-06-21Not applicableEU flag
OdefseyTablet, film coatedOralGilead Sciences Ireland Uc2016-06-21Not applicableEU flag
VemlidyTablet25 mg/1OralGilead Sciences, Inc.2016-11-10Not applicableUS flag
VemlidyTablet25 mgOralGilead Sciences2017-06-20Not applicableCanada flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
BiktarvyTenofovir alafenamide (25 mg) + Bictegravir (50 mg) + Emtricitabine (200 mg)TabletOralGilead Sciences2018-08-08Not applicableCanada flag
BiktarvyTenofovir alafenamide fumarate (25 mg/1) + Bictegravir sodium (50 mg/1) + Emtricitabine (200 mg/1)TabletOralGilead Sciences, Inc.2018-02-07Not applicableUS flag
DescovyTenofovir alafenamide (25 mg) + Emtricitabine (200 mg)TabletOralGilead Sciences2016-06-03Not applicableCanada flag
DescovyTenofovir alafenamide fumarate (25 mg/1) + Emtricitabine (200 mg/1)TabletOralGilead Sciences, Inc.2016-04-04Not applicableUS flag
DescovyTenofovir alafenamide fumarate (25 mg/1) + Emtricitabine (200 mg/1)TabletOralREMEDYREPACK INC.2017-02-16Not applicableUS flag
DescovyTenofovir alafenamide (10 mg) + Emtricitabine (200 mg)TabletOralGilead Sciences2016-06-03Not applicableCanada flag
GenvoyaTenofovir alafenamide (10 mg) + Cobicistat (150 mg) + Elvitegravir (150 mg) + Emtricitabine (200 mg)Tablet, film coatedOralGilead Sciences Ireland Uc2015-11-19Not applicableEU flag
GenvoyaTenofovir alafenamide fumarate (10 mg/1) + Cobicistat (150 mg/1) + Elvitegravir (150 mg/1) + Emtricitabine (200 mg/1)TabletOralA-S Medication Solutions2015-11-052018-07-31US flag
GenvoyaTenofovir alafenamide (10 mg) + Cobicistat (150 mg) + Elvitegravir (150 mg) + Emtricitabine (200 mg)TabletOralGilead Sciences2016-02-03Not applicableCanada flag
GenvoyaTenofovir alafenamide fumarate (10 mg/1) + Cobicistat (150 mg/1) + Elvitegravir (150 mg/1) + Emtricitabine (200 mg/1)TabletOralREMEDYREPACK INC.2017-06-06Not applicableUS flag

Categories

ATC Codes
J05AR19 — Emtricitabine, tenofovir alafenamide and rilpivirineJ05AR20 — Emtricitabine, tenofovir alafenamide and bictegravirJ05AR17 — Emtricitabine and tenofovir alafenamideJ05AF13 — Tenofovir alafenamideJ05AR22 — Emtricitabine, tenofovir alafenamide, darunavir and cobicistatJ05AR18 — Emtricitabine, tenofovir alafenamide, elvitegravir and cobicistat
Drug Categories
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

Chemical Identifiers

UNII
J4414G3BUK
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)[[email protected]](C)N[[email protected]](=O)(CO[[email protected]](C)CN1C=NC2=C(N)N=CN=C12)OC1=CC=CC=C1

References

General References
  1. 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. [PubMed:27438578]
  2. Grant PM, Cotter AG: Tenofovir and bone health. Curr Opin HIV AIDS. 2016 May;11(3):326-32. doi: 10.1097/COH.0000000000000248. [PubMed:26859637]
  3. 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. [PubMed:30460547]
  4. 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. [PubMed:29158666]
  5. 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. [PubMed:26640223]
  6. 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. [PubMed:26952360]
  7. 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. [PubMed:24508897]
  8. Wolpe P. and Howard J. (2007). Comprehensive Medicinal Chemistry II. Elsevier.
  9. Pubmed books [Link]
  10. FDA approvals [Link]
  11. FDA Approved Drug Products: Descovy (Emtricitabine and Tenofovir Alafenamide) Oral Tablets [Link]
  12. FDA Approved Drug Products: Bictegravir, Emtricitabine, and Tenofovir Alafenamide Oral Tablets [Link]
  13. FDA Approved Drug Products: Elvitegravir, Cobicistat, Emtricitabine, and Tenofovir Alafenamide Oral Tablets [Link]
  14. FDA Approved Drug Products: Darunavir, Cobicistat, Emtricitabine, and Tenofovir Alafenamide Oral Tablets [Link]
  15. Health Canada Approved Drug Products: Tenofovir Alafenamide Oral Tablets [Link]
  16. European Medicines Agency Assessment Report: Tenofovir Alafenamide [Link]
  17. FDA Press Announcements: FDA approves second drug to prevent HIV infection as part of ongoing efforts to end the HIV epidemic [Link]
KEGG Drug
D10428
PubChem Compound
9574768
PubChem Substance
310265191
ChemSpider
7849225
RxNav
1721603
ChEBI
90926
ChEMBL
CHEMBL2107825
ZINC
ZINC000100055899
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Tenofovir_alafenamide
AHFS Codes
  • 08:18.08.20 — Nucleoside and Nucleotide Reverse Transcriptase Inhibitors
FDA label
Download (1.08 MB)
MSDS
Download (254 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentHepatitis B Chronic Infection2
4Active Not RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections / Menopause / Osteoporosis1
4Active Not RecruitingTreatmentHuman Immunodeficiency Virus Type 1 (HIV-1) Infection1
4CompletedOtherCoinfection, HIV / Hepatitis C Viral Infection1
4CompletedOtherHealthy Volunteers1
4CompletedPreventionART / Human Immunodeficiency Virus (HIV) Infections1
4CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections4
4CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Severe Immunosuppression1
4Not Yet RecruitingBasic ScienceAbnormality of Adipose Tissue / Antiviral Drug Adverse Reaction / Body Fat Disorder / Cardiovascular Abnormalities / HIV-Associated Lipodystrophy Syndrome / Human Immunodeficiency Virus Type 1 (HIV-1) Infection / Vascular Diseases / Weight Changes1
4Not Yet RecruitingPreventionHCC Patients After Curative Treatment With Low HBV Viral Load1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Tablet, film coatedOral50 MG
Tablet, coatedOral50 mg
Tablet, film coatedOral200 MG
Tablet, coatedOral200 mg
Tablet, film coatedOral
Tablet, film coatedOral150 MG
Tablet, coatedOral150 mg
TabletOral
TabletOral200 MG
Tablet, film coatedOral
Tablet, film coatedOral800 MG
TabletOral25 mg/1
TabletOral25 mg
Tablet, coatedOral25 mg
Tablet
Tablet, coated25 mg
Tablet, film coatedOral25 MG
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US7800788No2010-09-212022-02-02US flag
US5914331Yes1999-06-222018-01-02US flag
US5814639Yes1998-09-292017-03-29US flag
US6642245Yes2003-11-042021-05-04US flag
US6703396Yes2004-03-092021-09-09US flag
US7470506Yes2008-12-302019-12-23US flag
US8597876Yes2013-12-032019-12-23US flag
US7700645Yes2010-04-202027-06-26US flag
US8518987Yes2013-08-272024-08-16US flag
US7125879No2006-10-242022-08-09US flag
US6838464No2005-01-042021-02-26US flag
US8080551No2011-12-202023-04-11US flag
US8101629No2012-01-242022-08-09US flag
US7067522No2006-06-272019-12-20US flag
US8148374No2012-04-032029-09-03US flag
US7635704No2009-12-222026-10-26US flag
US7176220No2007-02-132023-11-20US flag
US8981103No2015-03-172026-10-26US flag
US8633219No2014-01-212030-04-24US flag
US9296769No2016-03-292032-08-15US flag
US7803788No2010-09-282022-02-02US flag
US8754065No2014-06-172032-08-15US flag
US7390791No2008-06-242022-05-07US flag
US9891239No2018-02-132029-09-03US flag
US9889115Yes2018-02-132019-12-23US flag
US9216996No2015-12-222033-12-19US flag
US9708342No2017-07-182035-06-19US flag
US9732092No2017-08-152033-12-19US flag
US10039718No2018-08-072032-10-04US flag
US10385067No2019-08-202035-06-19US flag
US10548846No2016-11-082036-11-08US flag
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

    Learn more

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)104-107 ºC'MSDS'
boiling point (°C)640 ºC at 760 mmHg'MSDS'
water solubility4.86 mg/ml at 20 ºCProduct monograph. Gilead Sciences Canada
logP1.6Product monograph. Gilead Sciences Canada
pKa3.96Product monograph. Gilead Sciences Canada
Predicted Properties
PropertyValueSource
Water Solubility0.236 mg/mLALOGPS
logP1.49ALOGPS
logP1.88ChemAxon
logS-3.3ALOGPS
pKa (Strongest Acidic)11.36ChemAxon
pKa (Strongest Basic)5.12ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area143.48 Å2ChemAxon
Rotatable Bond Count12ChemAxon
Refractivity122.74 m3·mol-1ChemAxon
Polarizability47.88 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Kind
Protein
Organism
Human immunodeficiency virus 1
Pharmacological action
Yes
Actions
Inhibitor
General Function
Rna-dna hybrid ribonuclease activity
Specific Function
Not Available
Gene Name
pol
Uniprot ID
Q72547
Uniprot Name
Reverse transcriptase/RNaseH
Molecular Weight
65223.615 Da
References
  1. 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. [PubMed:24741339]
  2. 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. [PubMed:26640223]
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
  1. 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. [PubMed:24741339]
  2. 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. [PubMed:26640223]
Kind
Protein
Organism
Human herpesvirus 2 (strain 186)
Pharmacological action
No
Actions
Inhibitor
General Function
Not Available
Specific Function
Dna binding
Gene Name
Not Available
Uniprot ID
I6TLU5
Uniprot Name
DNA polymerase
Molecular Weight
137296.405 Da
References
  1. 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. [PubMed:24741339]
  2. 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. [PubMed:26640223]

Enzymes

Kind
Protein
Organism
Not Available
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
  1. 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. [PubMed:27438578]
  2. 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. [PubMed:30460547]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Triglyceride lipase activity
Specific Function
Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Hydrolyzes aromatic and aliphatic esters, but has no catalytic activity toward amides or a fatty acy...
Gene Name
CES1
Uniprot ID
P23141
Uniprot Name
Liver carboxylesterase 1
Molecular Weight
62520.62 Da
References
  1. 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. [PubMed:27438578]
  2. 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. [PubMed:30460547]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. FDA Approved Drug Products: Bictegravir, Emtricitabine, and Tenofovir Alafenamide Oral Tablets [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Nucleoside diphosphate kinase activity
Specific Function
Catalyzes the reversible transfer of the terminal phosphate group between ATP and AMP. Also displays broad nucleoside diphosphate kinase activity. Plays an important role in cellular energy homeost...
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
Atp binding
Specific 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 ...
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
Ribosomal small subunit binding
Specific 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-sit...
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
Transcription factor activity, sequence-specific dna binding
Specific Function
Major role in the synthesis of nucleoside triphosphates other than ATP. Negatively regulates Rho activity by interacting with AKAP13/LBC. Acts as a transcriptional activator of the MYC gene; binds ...
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
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. 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. [PubMed:30460547]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. 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. [PubMed:28689442]
  2. 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. [PubMed:29649076]
  3. 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. [PubMed:27216057]
  4. 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. [PubMed:25870059]
  5. 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. [PubMed:27438578]
  6. HIV insite, UCSF: Tenofovir Alafenamide [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Atpase activity, coupled to transmembrane movement of substances
Specific Function
May be an organic anion pump relevant to cellular detoxification.
Gene Name
ABCC4
Uniprot ID
O15439
Uniprot Name
Multidrug resistance-associated protein 4
Molecular Weight
149525.33 Da
References
  1. 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. [PubMed:27438578]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one ...
Gene Name
SLC22A6
Uniprot ID
Q4U2R8
Uniprot Name
Solute carrier family 22 member 6
Molecular Weight
61815.78 Da
References
  1. 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. [PubMed:27438578]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenad...
Gene Name
SLC22A8
Uniprot ID
Q8TCC7
Uniprot Name
Solute carrier family 22 member 8
Molecular Weight
59855.585 Da
References
  1. 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. [PubMed:27438578]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
References
  1. 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. [PubMed:30460547]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. 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. [PubMed:29158666]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
Gene Name
SLCO1B3
Uniprot ID
Q9NPD5
Uniprot Name
Solute carrier organic anion transporter family member 1B3
Molecular Weight
77402.175 Da
References
  1. 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. [PubMed:29158666]

Drug created on November 08, 2015 14:16 / Updated on October 21, 2020 01:55

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