GS-7340 fumarate

Category	Reverse Transcriptases (RTs)
CAS	379270-38-9
Description	Tenofovir alafenamide fumarate, also known as Tenofovir alafenamide hemifumarate; TAF, GS-7340, is a nucleotide reverse transcriptase inhibitor and a novel prodrug of tenofovir. It is under development by Gilead Sciences for use in the treatment of HIV infection. Closely related to the commonly used reverse-transcriptase inhibitor tenofovir disoproxil fumarate (Viread), Tenofovir alafenamide has greater antiviral activity and better distribution into lymphoid tissues than that agent. Gilead has announced a phase 3 clinical trial evaluating a single-tablet regimen combining GS-7340 with cobicistat, emtricitabine and elvitegravir and plans to coformulate the drug with cobicistat, emtricitabine and the protease inhibitor darunavir. In a 48 week study comparing Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate to elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide fumarate, the results showed the prodrug to be non inferior to the established agent, but at much lower dosages and with lower incidence of adverse side effects such as impaired kidney function.

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Product Information

Synonyms	GS-7340 fumarate; GS 7340 fumarate; GS7340 fumarate; (S)-isopropyl 2-(((S)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(phenoxy)phosphoryl)amino)propanoate fumarate; TAF; GS734; GS-734; GS 7340; Tenofovir alafenamide fumarate; trade name: Genvoya
Molecular Weight	592.54
Molecular Formula	C25H33N6O9P
Canonical SMILES	C[C@@H](C(OC(C)C)=O)N[P@@](OC1=CC=CC=C1)(CO[C@@H](CN2C=NC3=C(N=CN=C23)N)C)=O.O=C(/C=C/C(O)=O)O
InChI	1S/C21H29N6O5P.C4H4O4/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;5-3(6)1-2-4(7)8/h5-9,11-12,14-16H,10,13H2,1-4H3,(H,26,29)(H2,22,23,24);1-2H,(H,5,6)(H,7,8)/b;2-1+/t15-,16+,33?;/m1./s1
InChIKey	MEJAFWXKUKMUIR-WIUYAKJJSA-N
Purity	>98%
Solubility	In vitro: 10 mM in DMSO
Appearance	White to off-white solid powder
Storage	4°C, sealed storage, away from moisture * In solvent : -80°C, 6 months -20°C, 1 month (sealed storage, away from moisture)
Complexity	799
Exact Mass	592.20466365
In Vitro	Tenofovir alafenamide fumarate (GS-7340 fumarate) antiviral activities are similar across all cell types, ranging from 5 to 7 nM, while the CC50 varies from 4.7 to 42 μM for MT-4 and MT-2 cells, respectively. The antiviral activity of TAF is evaluated against a panel of HIV-1 and HIV-2 isolates, including HIV-1 group M subtypes A to G, as well as group N and O isolates. Overall, for the 29 primary HIV-1 isolates tested in PBMCs, TAF EC50s range from 0.1 to 12 nM, with a mean EC50 of 3.5 nM compared to a mean EC50 of 11.8 nM for AZT, which is used as an internal control. For the HIV-2 isolates, the mean EC50s are 1.8 nM for TAF and 6.4 nM for AZT.
In Vivo	Tenofovir alafenamide fumarate (GS-7340 fumarate) is an amidate prodrug of Tenofovir with good oral bioavailability and increases plasma stability compared to Tenofovir disoproxil fumarate (TDF).
PSA	227.89000
Target	HIV; Reverse Transcriptase