Identification

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Name
Tenofovir
Accession Number
DB14126
Type
Small Molecule
Groups
Experimental, Investigational
Description

Tenofovir is an acyclic nucleotide diester analog of adenosine monophosphate.4 In the most strict sense and due to the fact that it presents a phosphate group bound to the nitrogenous base, it is determined as an actual nucleotide analog.4 The antiviral activities of tenofovir were first reported in 1993 and this agent was commercially available since 2008 in the form of tenofovir disoproxil and tenofovir alafenamide in order to obtain oral bioavailability.3,6

Structure
Thumb
Synonyms
  • (R)-PMPA
  • Anhydrous tenofovir
  • Tenofovir (anh.)
  • Tenofovir (anhydrous)
  • Tenofovir anhydrous
External IDs
GS 1275 / GS-1275
Product Ingredients
IngredientUNIICASInChI Key
Tenofovir hydrate99YXE507IL206184-49-8PINIEAOMWQJGBW-FYZOBXCZSA-N
Categories
UNII
W4HFE001U5
CAS number
147127-20-6
Weight
Average: 287.2123
Monoisotopic: 287.078340473
Chemical Formula
C9H14N5O4P
InChI Key
SGOIRFVFHAKUTI-ZCFIWIBFSA-N
InChI
InChI=1S/C9H14N5O4P/c1-6(18-5-19(15,16)17)2-14-4-13-7-8(10)11-3-12-9(7)14/h3-4,6H,2,5H2,1H3,(H2,10,11,12)(H2,15,16,17)/t6-/m1/s1
IUPAC Name
({[(2R)-1-(6-amino-9H-purin-9-yl)propan-2-yl]oxy}methyl)phosphonic acid
SMILES
C[C@H](CN1C=NC2=C1N=CN=C2N)OCP(O)(O)=O

Pharmacology

Indication

Tenofovir has been shown to be effective against HIV, herpes simplex virus-2, and hepatitis B virus.5

To know more about the specific product indications, please visit the information in the orally available forms of tenofovir, tenofovir alafenamide and tenofovir disoproxil.

Pharmacodynamics

Tenofovir has been shown to be highly effective in patients that have never had an antiretroviral therapy and it seemed to have lower toxicity than other antivirals such as stavudine. In phase 3 clinical trials, tenofovir presented a similar efficacy than efavirenz in treatment-naive HIV patients.5 In hepatitis B infected patients, after one year of tenofovir treatment, the viral DNA levels were undetectable.6

Mechanism of action

Once tenofovir is activated by a bi-phosphorylation it acts as an antiviral acyclic nucleoside phosphonate. It is a potent inhibitor of the viral reverse transcriptase with an inhibitory constant of approximately 0.022 micromolar.3

Once activated, tenofovir acts with different mechanisms including the inhibition of viral polymerase causing chain termination and the inhibition of viral synthesis.12 All these activities are attained by its competition with deoxyadenosine 5'-triphosphate in the generation of new viral DNA. Once tenofovir is incorporated in the chain, it induces a chain termination which in order inhibits viral replication.5 The safety of tenofovir relies on its low affinity towards the cellular DNA polymerase including the mitochondrial DNA polymerase gamma.11

TargetActionsOrganism
AReverse transcriptase/RNaseH
inhibitor
Human immunodeficiency virus 1
AReverse transcriptase
inhibitor
HBV
ADNA polymerase
inhibitor
Human herpesvirus 2 (strain 186)
Absorption

Tenofovir as the active moiety presents a very low bioavailability when orally administered. Hence, the administration of this active agent is required to be under its two prodrug forms, tenofovir disoproxil and tenofovir alafenamide. This reduced absorption is suggested to be related to the presence of two negative charges among its structure. This negative charge limits its cellular penetration, and its passive diffusion across cellular membranes and intestinal mucosa hindering its availability for oral administration.1

Intravenous tenofovir has been shown to produce a maximum plasma concentration of 2500 ng/ml with an AUC of 4800 ng.h/ml.3

Volume of distribution

Accumulation of tenofovir in plasma is related to the presence of nephrotoxic effects.1 It is reported that tenofovir presents a volume of distribution of 0.813 L/kg.7

Protein binding

Tenofovir is minimally bound to plasma proteins and only about 7.2% of the administered dose is found in the bound state.7

Metabolism

Tenofovir activation is performed by a bi-phosphorylation which in order forms the biologically active compound, tenofovir biphosphate.1 This metabolic activation has been shown to be performed in hepG2 cells and human hepatocytes.8 After activation, it does present minimal metabolic processing by the cytochrome enzyme isoenzyme CYP3A.13

Route of elimination

Tenofovir is eliminated in the urine by tubular secretion and glomerular filtration. The elimination of this compound is driven by the activity of the human organic anion transporters 1 and 3 and its secretion is mainly ruled by the activity of the multidrug resistance-associated protein 4.1

Half life

The reported half-life of tenofovir is of 32 hours.2

Clearance

The clearance of tenofovir is highly dependent on the patient renal stage and hence the clearance rate in patients with renal impairment is reported to be of 134 ml/min while in patients with normal function the clearance rate can be of 210 ml/min.9

Toxicity

There haven't been reports regarding the LD50 of the parent compound nor the effects of an overdose. However, based on the reports with the derivative that most rapidly transforms into tenofovir, tenofovir disoproxil, it is recommended to monitor overdose patients. As well, it is widely known that tenofovir is efficiently removed by hemodialysis.10

Administration of high doses of tenofovir has been reported to produce bone toxicity reported as osteomalacia and reduced bone mineral density and to produce some degree of renal toxicity.14

To know more about the carcinogenicity and mutagenic potential of tenofovir, as well as the effect on fertility, please visit the drug entries for the derivatives tenofovir disoproxil and tenofovir alafenamide.

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
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Tenofovir.
6-Deoxyerythronolide BThe metabolism of Tenofovir can be decreased when combined with 6-Deoxyerythronolide B.
7-ethyl-10-hydroxycamptothecinThe metabolism of Tenofovir can be decreased when combined with 7-ethyl-10-hydroxycamptothecin.
9-aminocamptothecinThe metabolism of Tenofovir can be decreased when combined with 9-aminocamptothecin.
AbacavirTenofovir may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbataceptThe metabolism of Tenofovir can be increased when combined with Abatacept.
AbemaciclibThe serum concentration of Tenofovir can be increased when it is combined with Abemaciclib.
AcalabrutinibThe metabolism of Tenofovir can be decreased when combined with Acalabrutinib.
AcarboseTenofovir may decrease the excretion rate of Acarbose which could result in a higher serum level.
AcebutololThe serum concentration of Tenofovir can be increased when it is combined with Acebutolol.
Additional Data Available
  • Extended Description
    Extended Description

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

    Learn more
  • 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
Not Available

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. 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]
  3. 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]
  4. Margolis AM, Heverling H, Pham PA, Stolbach A: A review of the toxicity of HIV medications. J Med Toxicol. 2014 Mar;10(1):26-39. doi: 10.1007/s13181-013-0325-8. [PubMed:23963694]
  5. 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]
  6. Ridruejo E: Treatment of chronic hepatitis B in clinical practice with entecavir or tenofovir. World J Gastroenterol. 2014 Jun 21;20(23):7169-80. doi: 10.3748/wjg.v20.i23.7169. [PubMed:24966587]
  7. Fung HB, Stone EA, Piacenti FJ: Tenofovir disoproxil fumarate: a nucleotide reverse transcriptase inhibitor for the treatment of HIV infection. Clin Ther. 2002 Oct;24(10):1515-48. [PubMed:12462284]
  8. Delaney WE 4th, Ray AS, Yang H, Qi X, Xiong S, Zhu Y, Miller MD: Intracellular metabolism and in vitro activity of tenofovir against hepatitis B virus. Antimicrob Agents Chemother. 2006 Jul;50(7):2471-7. doi: 10.1128/AAC.00138-06. [PubMed:16801428]
  9. Kearney BP, Yale K, Shah J, Zhong L, Flaherty JF: Pharmacokinetics and dosing recommendations of tenofovir disoproxil fumarate in hepatic or renal impairment. Clin Pharmacokinet. 2006;45(11):1115-24. doi: 10.2165/00003088-200645110-00005. [PubMed:17048975]
  10. Izzedine H, Launay-Vacher V, Jullien V, Aymard G, Duvivier C, Deray G: Pharmacokinetics of tenofovir in haemodialysis. Nephrol Dial Transplant. 2003 Sep;18(9):1931-3. doi: 10.1093/ndt/gfg327. [PubMed:12937248]
  11. Sivapalasingam S., Steigbigel N. (2015). Mandell, Douglas and Bennett's Principles and practice of infectious diseases (8th ed.). Elsevier.
  12. Pubmed books [Link]
  13. FDA Approved Drug Products: Bictegravir, Emtricitabine, and Tenofovir Alafenamide Oral Tablets [Link]
  14. FDA label [Link]
External Links
Human Metabolome Database
HMDB0014445
ChemSpider
408154
ChEBI
63625
ChEMBL
CHEMBL483
PharmGKB
PA10204
HET
TFO
Wikipedia
Tenofovir_disoproxil
PDB Entries
1t03
MSDS
Download (79.7 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingOtherHIV Prevention1
1CompletedNot AvailableHIV Prevention1
1CompletedNot AvailableHuman Immunodeficiency Virus (HIV)1
1CompletedNot AvailableHuman Immunodeficiency Virus (HIV) Infections2
1CompletedBasic ScienceHIV Prevention / Human Immunodeficiency Virus (HIV) Infections1
1CompletedBasic ScienceHuman Immunodeficiency Virus (HIV) Infections1
1CompletedHealth Services ResearchHuman Immunodeficiency Virus (HIV)1
1CompletedOtherPharmacodynamics of 1% Tenofovir Gel Following Coitus / Pharmacokinetics of 1% Tenofovir Gel Following Coitus1
1CompletedOtherRectal Microbicides1
1CompletedPrevention18-30 Years of Age / High Risk MSM / HIV Negative1
1CompletedPreventionAnti-Infective Agents / Anti-Retroviral Agents / Contraceptive Usage1
1CompletedPreventionHIV Prevention3
1CompletedPreventionHuman Immunodeficiency Virus (HIV)1
1CompletedPreventionHuman Immunodeficiency Virus (HIV) Infections4
1CompletedPreventionPrevention1
1CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection1
1CompletedTreatmentContraception / Human Immunodeficiency Virus (HIV)1
1CompletedTreatmentHealthy Volunteers1
1CompletedTreatmentHepatitis B Chronic Infection1
1CompletedTreatmentHuman Immunodeficiency Virus (HIV)1
1CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections2
1CompletedTreatmentViral Hepatitis B1
1Not Yet RecruitingPreventionHIV Prevention / Human Immunodeficiency Virus Infection(HIV)/Acquired Immunodeficiency Syndrome (AIDS)1
1RecruitingTreatmentHuman Immunodeficiency Virus (HIV)1
1TerminatedTreatmentViral Hepatitis B2
1Unknown StatusBasic ScienceAtazanavir1
1, 2CompletedTreatmentHepatitis B Chronic Infection1
1, 2Unknown StatusTreatmentHepatitis B Chronic Infection1
2Active Not RecruitingTreatmentHepatitis B Chronic Infection1
2Active Not RecruitingTreatmentHuman Immunodeficiency Virus (HIV)1
2Active Not RecruitingTreatmentViral Hepatitis B / Virus Hepatitis1
2CompletedNot AvailableHuman Immunodeficiency Virus (HIV)1
2CompletedPreventionHIV Seropositivity1
2CompletedPreventionHepatitis B Chronic Infection / Human Immunodeficiency Virus (HIV) Infections1
2CompletedPreventionHuman Immunodeficiency Virus (HIV) Infections2
2CompletedPreventionHuman Immunodeficiency Virus (HIV) Infections / Pregnancy1
2CompletedTreatmentAcquired Immune Deficiency Syndrome (AIDS) / Human Immunodeficiency Virus (HIV) Infections1
2CompletedTreatmentAcute HIV Infection / HIV CNS Involvement1
2CompletedTreatmentAntiretroviral Therapies / Human Immunodeficiency Virus (HIV) Infections / Human Immunodeficiency Virus Infection(HIV)/Acquired Immunodeficiency Syndrome (AIDS)1
2CompletedTreatmentHepatitis B Chronic Infection1
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections3
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Human Immunodeficiency Virus Type 1 (HIV-1)1
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Human Immunodeficiency Virus Type 1 (HIV-1) Infection1
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Progressive Multifocal Leukoencephalopathy1
2CompletedTreatmentInfectious Diseases1
2Enrolling by InvitationPreventionAnti-Retroviral Agent / Contraception / Human Immunodeficiency Virus (HIV) / Prevention1
2RecruitingTreatmentHepatitis B Chronic Infection1
2TerminatedTreatmentHuman Immunodeficiency Virus (HIV) Infections2
2TerminatedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Human Immunodeficiency Virus Infection(HIV)/Acquired Immunodeficiency Syndrome (AIDS)1
2TerminatedTreatmentViral Hepatitis B4
2Unknown StatusPreventionHuman Immunodeficiency Virus (HIV) / Viral Hepatitis B1
2Unknown StatusTreatmentHuman Immunodeficiency Virus (HIV) Infections / Tuberculosis Infection1
2WithdrawnPreventionHuman Immunodeficiency Virus (HIV) Infections1
2, 3CompletedPreventionHuman Immunodeficiency Virus (HIV)1
2, 3CompletedTreatment2- HIV Infection1
2, 3CompletedTreatmentHuman Immunodeficiency Virus (HIV) / Pregnancy1
3Active Not RecruitingTreatmentChronic Hepatitis B e Antigen Negative / Chronic Hepatitis B e Antigen Positive1
3Active Not RecruitingTreatmentHepatitis B Chronic Infection1
3Active Not RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections1
3Active Not RecruitingTreatmentHuman Immunodeficiency Virus Type 1 (HIV-1) Infection / Tuberculosis Infection1
3CompletedPreventionHIV Prevention1
3CompletedTreatmentHepatitis B Chronic Infection1
3CompletedTreatmentHepatitis B Virus (HBV)1
3CompletedTreatmentHepatitis D, Chronic1
3CompletedTreatmentHuman Immunodeficiency Virus (HIV)3
3CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections5
3CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Human Immunodeficiency Virus Type 1 (HIV-1) Infection1
3CompletedTreatmentHuman Immunodeficiency Virus (HIV) / Human Immunodeficiency Virus (HIV) Infections1
3CompletedTreatmentHuman Immunodeficiency Virus Type 1 (HIV-1) Infection2
3Not Yet RecruitingTreatmentHIV-1-infection1
3Not Yet RecruitingTreatmentHuman Immunodeficiency Virus (HIV)1
3RecruitingPreventionAIDS/HIV problem1
3RecruitingTreatmentHepatitis B Chronic Infection2
3RecruitingTreatmentHuman Immunodeficiency Virus (HIV)1
3TerminatedTreatmentHBe Negative Chronic Hepatitis B / Hepatitis B Viral Infection1
3TerminatedTreatmentHepatitis B Chronic Infection1
3TerminatedTreatmentHuman Immunodeficiency Virus (HIV)1
3TerminatedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
3Unknown StatusTreatmentAcquired Immune Deficiency Syndrome (AIDS) / Human Immunodeficiency Virus (HIV) Infections1
4Active Not RecruitingPreventionHuman Immunodeficiency Virus (HIV) / Syphilis1
4Active Not RecruitingTreatmentHepatitis B Chronic Infection1
4Active Not RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections1
4Active Not RecruitingTreatmentViral Hepatitis B1
4CompletedNot AvailableHealthy Volunteers1
4CompletedNot AvailableHuman Immunodeficiency Virus (HIV)1
4CompletedNot AvailableHuman Immunodeficiency Virus (HIV) Infections1
4CompletedNot AvailableHuman Immunodeficiency Virus (HIV) / Proteinuria1
4CompletedDiagnosticCardiovascular Disease (CVD) / HIV-Associated Lipodystrophy Syndrome1
4CompletedOtherHuman Immunodeficiency Virus (HIV)1
4CompletedPreventionHIV Nonoccupational Post-exposure Prophylaxis in Men Who Have Sex With Men1
4CompletedPreventionHuman Immunodeficiency Virus (HIV)1
4CompletedPreventionHuman Immunodeficiency Virus (HIV) Infections2
4CompletedTreatmentHIV Associated Neurocognitive Disorders (HAND) / Neurocognitive Decline1
4CompletedTreatmentHepatitis B Chronic Infection2
4CompletedTreatmentHepatitis B Coinfection / Human Immunodeficiency Virus (HIV) Infections1
4CompletedTreatmentHerpes Simplex Type II1
4CompletedTreatmentHuman Immunodeficiency Virus (HIV)3
4CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections5
4CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Human Immunodeficiency Virus Type 1 (HIV-1) Infection1
4CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Viral Hepatitis B1
4CompletedTreatmentHuman Immunodeficiency Virus (HIV) / Human Immunodeficiency Virus (HIV) Infections1
4CompletedTreatmentHuman Immunodeficiency Virus Type 1 (HIV-1)2
4RecruitingTreatmentAcute HIV Infection1
4RecruitingTreatmentHepatitis, Chronic1
4RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections2
4TerminatedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
4TerminatedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Tuberculosis Infection1
4TerminatedTreatmentMetabolic Complications / Mitochondrial Toxicity1
4Unknown StatusTreatmentCirrhosis Due to Hepatitis B1
4Unknown StatusTreatmentHepatitis B Chronic Infection1
4Unknown StatusTreatmentHuman Immunodeficiency Virus (HIV) Infections1
4Unknown StatusTreatmentHuman Immunodeficiency Virus (HIV) / Human Immunodeficiency Virus (HIV) Infections1
4WithdrawnTreatmentHepatitis B Chronic Infection1
Not AvailableCompletedNot AvailableHIV-infected Thai Children1
Not AvailableCompletedNot AvailableHuman Immunodeficiency Virus (HIV)1
Not AvailableCompletedNot AvailableHuman Immunodeficiency Virus Type 1 (HIV-1) Infection1
Not AvailableCompletedNot AvailableThis Study is Designed to Collect Treatment Data of Thai Children on Third Line ARV Therapy1
Not AvailableCompletedPreventionMicrobicide Applicator1
Not AvailableCompletedTreatmentAcute on Chronic Liver Failure1
Not AvailableCompletedTreatmentAnti-Retroviral Agents / Dyslipidemias / Efavirenz / HIV-1-infection / Rilpivirine / Sustained Virologic Response1
Not AvailableCompletedTreatmentAntiretroviral Treatment Outcomes1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Proteinuria1
Not AvailableCompletedTreatmentSpontaneous Reactivation of Hepatitis B1
Not AvailableEnrolling by InvitationNot AvailableThe Safety of Anti-viral Drugs Used in Late Pregnancy1
Not AvailableNot Yet RecruitingNot AvailableHIV-I Infection1
Not AvailableNot Yet RecruitingPreventionHuman Immunodeficiency Virus (HIV)1
Not AvailableRecruitingNot AvailableAcquired Immune Deficiency Syndrome (AIDS)1
Not AvailableRecruitingNot AvailableHepatitis B Chronic Infection1
Not AvailableRecruitingNot AvailableHuman Immunodeficiency Virus Infection(HIV)/Acquired Immunodeficiency Syndrome (AIDS) / Inflammation Vagina / Menopause1
Not AvailableRecruitingTreatmentHepatitis B, Chronic1
Not AvailableRecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections1
Not AvailableTemporarily Not AvailableNot AvailableHepatitis B Chronic Infection1
Not AvailableUnknown StatusTreatmentHBV Coinfection / Human Immunodeficiency Virus (HIV) Infections1
Not AvailableWithdrawnNot AvailableHIV-infected Patients1
Not AvailableWithdrawnTreatmentHBV1
Not AvailableWithdrawnTreatmentHepatitis B Chronic Infection1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)279 ºC'ChemicalBook'
boiling point (°C)616 ºC at 760 mmHg'MSDS'
water solubility13.4 mg/ml'ChemicalBook'
logP-1.6Lastours V. et al. 2011. Antimicrob Agents Chemother.
pKa3.8 and 6.7Zhang T. et al. 2012. Eur J Pharm Biopharm.
Predicted Properties
PropertyValueSource
Water Solubility1.87 mg/mLALOGPS
logP-1.5ALOGPS
logP-3.4ChemAxon
logS-2.2ALOGPS
pKa (Strongest Acidic)1.35ChemAxon
pKa (Strongest Basic)3.74ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area136.38 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity67.54 m3·mol-1ChemAxon
Polarizability25.54 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-000i-0290000000-3e1938b3d02b375e35df
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-001r-1930000000-d365f36771addeb5b51c
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-001i-2900000000-c8f91e6bb9d4588f055d
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-001i-2900000000-099f967e8f8229f1fb82
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-001i-3900000000-521761795a56429a8f51
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-06si-5900000000-b88fc7e5619f18889624
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-000i-0090000000-e85e6b9ea88e6c214687
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-000i-0190000000-405fbe60309faffed10c
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-004r-0950000000-d7cec4ba580879c76061
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-004i-0910000000-f2abf612e945d8c69371
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-056r-1900000000-c48435c099065334ef3e
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0570-1900000000-7b90db7cba32420df6d1

Taxonomy

Description
This compound belongs to the class of organic compounds known as 6-aminopurines. These are purines that carry an amino group at position 6. Purine is a bicyclic aromatic compound made up of a pyrimidine ring fused to an imidazole ring.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Imidazopyrimidines
Sub Class
Purines and purine derivatives
Direct Parent
6-aminopurines
Alternative Parents
Aminopyrimidines and derivatives / N-substituted imidazoles / Imidolactams / Organic phosphonic acids / Heteroaromatic compounds / Azacyclic compounds / Primary amines / Organopnictogen compounds / Organophosphorus compounds / Organooxygen compounds
show 2 more
Substituents
6-aminopurine / Aminopyrimidine / N-substituted imidazole / Pyrimidine / Imidolactam / Azole / Imidazole / Organophosphonic acid / Organophosphonic acid derivative / Heteroaromatic compound
show 12 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
phosphonic acids (CHEBI:63625)

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
Yes
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. 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]
  2. 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]
Kind
Protein
Organism
Human herpesvirus 2 (strain 186)
Pharmacological action
Yes
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
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
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
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

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
No
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. 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]
  2. Droste JA, Verweij-van Wissen CP, Kearney BP, Buffels R, Vanhorssen PJ, Hekster YA, Burger DM: Pharmacokinetic study of tenofovir disoproxil fumarate combined with rifampin in healthy volunteers. Antimicrob Agents Chemother. 2005 Feb;49(2):680-4. doi: 10.1128/AAC.49.2.680-684.2005. [PubMed:15673751]
  3. 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]
  4. 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]
  5. Moss DM, Domanico P, Watkins M, Park S, Randolph R, Wring S, Rajoli RKR, Hobson J, Rannard S, Siccardi M, Owen A: Simulating Intestinal Transporter and Enzyme Activity in a Physiologically Based Pharmacokinetic Model for Tenofovir Disoproxil Fumarate. Antimicrob Agents Chemother. 2017 Jun 27;61(7). pii: AAC.00105-17. doi: 10.1128/AAC.00105-17. Print 2017 Jul. [PubMed:28416547]
  6. 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]
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
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]

Drug created on June 24, 2018 10:23 / Updated on November 02, 2019 04:42