General
Preferred name
TENOFOVIR ALAFENAMIDE
Synonyms
Tenofovir alafenamide hemifumarate ()
GS-7340 (hemifumarate) ()
GS-7340 ()
TENOFOVIR ALAFENAMIDE FUMARATE ()
Genvoya-tenofovir alafenamide ()
GS-7340 (fumarate) ()
Tenofovir Alafenamide (GS-7340) ()
TAF fumarate, GS-7340 fumarate ()
TAF hemifumarate, GS-7340 hemifumarate ()
Vemlidy ()
GS-734003 ()
GS-7340 HEMIFUMARATE ()
GS-7340-03 ()
P&D ID
PD009264
CAS
1392275-56-7
379270-37-8
379270-38-9
Tags
prodrug
natural product
drug
available
Approved by
PMDA
EMA
FDA
First approval
2015
2014
Drug Status
approved
Drug indication
Hepatitis B virus infection
Human immunodeficiency virus infection
Chronic hepatitis B infection
Max Phase
Phase 4
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
PHARMACODYNAMICS
Tenofovir alafenamide has been shown to be a potent inhibitor of the hepatitis B virus replication.[A178249]; ; 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.[A178060]; ; In clinical trials, tenofovir alafenamide was shown to present 5-fold more potent antiviral activity against HIV-1 when compared to tenofovir disoproxil.[A178060]
HALF-LIFE
The reported half-life for tenofovir alafenamide is of 0.51 hours.[A178231]
MOA
Tenofovir alafenamide presents even a 91% lower plasma concentration with an intracellular presence of about 20-fold higher when compared to [tenofovir disoproxil].[A178219] It is a great alternative to obtain a higher potency against viral-target cells. This is due to its prolonged systemic exposure and its driven higher intracellular accumulation of the active metabolite tenofovir diphosphate.[A18473]; ; Tenofovir alafenamide mechanism of action has been studied and it has been reported that this prodrug presents a high accumulation in peripheral blood mononuclear cells when compared to red blood cells.[A18473]; ; Once activated, tenofovir acts with different mechanisms including the inhibition of viral polymerase causing chain termination and the inhibition of viral synthesis.[L6241] To know more about the specific mechanism of action of the active form, please visit the drug entry of [tenofovir].
ROE
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.[A178060]
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%.[L6286]; ; 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.[L6286]
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.[A178060]; ; After activation, tenofovir is further processed and after 1-2 days, it is detected in plasma almost completely transformed to uric acid.[A178060]
ABSORPTION
As compared to the parent molecule, [tenofovir], tenofovir alafenamide presents a lipophilic group that masks the negative charge of the parent moiety which in order improves its oral bioavailability.[A178060]; ; Due to the molecular properties of tenofovir alafenamide, this molecule is highly stable in the 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.[A178060, A18473] Once inside the body, tenofovir alafenamide enters hepatocytes by passive diffusion regulated by the organic anion transporters 1B1 and 1B3 for its activation.[A178249]; ; Administration of tenofovir alafenamide concomitantly with a high-fat meal results in an increase of about 65% in its internal exposure.[L6286]
INDICATION
Tenofovir alafenamide is indicated for the treatment of chronic hepatitis B in adult patients with compensated liver disease.[L6241]; ; In combination with [emtricitabine] and other antiretrovirals, it is indicated for the treatment of HIV-1 infection in patients with a weight higher than 35 kg. When combined with antiretrovirals other than protease inhibitors that require a CYP3A inhibitor, it can be used in pediatric patients weighing between 25 and 35 kg.[L4388]; ; 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.[L6277] ; ; 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.[L6280]; ; Lastly, 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.[L6283]
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Cell lines
0
Organisms
2
Compound Sets
16
AdooQ Bioactive Compound Library
Axon Medchem Screening Library
Cayman Chemical Bioactives
ChEMBL Approved Drugs
ChEMBL Drugs
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP Approved Drugs
Natural product-based probes and drugs
ReFrame library
Selleckchem Bioactive Compound Library
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
50
Molecular Weight
476.19
Hydrogen Bond Acceptors
10
Hydrogen Bond Donors
2
Rotatable Bonds
11
Ring Count
3
Aromatic Ring Count
3
cLogP
2.97
TPSA
143.48
Fraction CSP3
0.43
Chiral centers
3.0
Largest ring
6.0
QED
0.31
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Pathway
Microbiology&virology
Proteases/Proteasome
Anti-infection
Target
HIV-1
Reverse Transcriptase
HIV-1 RT inhibitor
HIV
Biosynthetic Origin
Nucleoside
Therapeutic Indication
Antiviral
Therapeutic Class
Antiviral Agent
Source data
