"目录号: HY-15232B
Anti-infection-
GS-7340 (Tenofovir alafenamide) hemifumarate 是 Tenofovir (TFV) 的前体，Tenofovir (TFV) 是一种HIV-1核苷酸逆转录酶抑制剂。
HIVReverse Transcriptase
相关产品
Dolutegravir-Maraviroc-Elvitegravir-Atazanavir sulfate-Tenofovir Disoproxil Fumarate-Tipranavir-Triciribine-Emtricitabine-Efavirenz-Miltefosine-Ritonavir-Delavirdine mesylate-Lamivudine-Abacavir-BI 224436-
生物活性
Description
GS-7340 (Tenofovir alafenamide) hemifumarate is an investigational oral prodrug of theHIV-1nucleotide reverse transcriptase inhibitor Tenofovir (TFV).
IC50& Target
HIV-1, NRTIs[1]
In Vitro
Tenofovir disoproxil fumarate (TDF) serves as a control for CatA-independent prodrug activation. Baseline antiviral activities (mean EC50±standard deviation) obtained in the absence of a protease inhibitors (PI) are determined from 6 independent donors for GS-7340 (EC50=5.3±1.2 nM) and TDF (EC50=2.8±1.1 nM) and are used to calculate fold change EC50s from four independent donors under conditions of PI pretreatment[1]. GS-7340 antiviral activities are similar across all cell types, ranging from 5 to 7 nM, while the CC50varies 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 EC50of 3.5 nM compared to a mean EC50of 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[2].
In Vivo
GS-7340 is an amidate prodrug of Tenofovir with good oral bioavailability and increases plasma stability compared to Tenofovir disoproxil fumarate (TDF)[1].
References
[1].Birkus G, et al. Intracellular Activation of Tenofovir Alafenamide and the Effect of Viral and Host Protease Inhibitors. Antimicrob Agents Chemother. 2015 Oct 26;60(1):316-22.
[2].Callebaut C, et al. In Vitro Virology Profile of Tenofovir Alafenamide, a Novel Oral Prodrug of Tenofovir with Improved Antiviral Activity Compared to That of Tenofovir Disoproxil Fumarate. Antimicrob Agents Chemother. 2015 Oct;59(10):5909-16.