Amprenavir

Amprenavir (VX-478) is a HIV protease inhibitor (Ki=0.6 nM) used to treat HIV infection. Amprenavir is also a SARS-CoV 3CL^pro inhibitor with an IC₅₀ of 1.09 μM. IC50 & Target:IC50 Value: 0.6 nM (Ki); Against wild-type clinical HIV isolates:14.6 +/- 12.5 ng/mL (mean +/- SD) [1]. Target: HIV protease In Vitro: Amprenavir has an enzyme inhibition constant (K_i = 0.6 nM) that falls within the Ki range of the other protease inhibitors. Amprenavir's in vitro 50% inhibitory concentration (IC₅₀) against wild-type clinical HIV isolates is 14.6 ng/mL^[1]. Amprenavir had direct inhibitory effects on invasion of Huh-7 hepatocarcinoma cell lines, inhibiting MMP proteolytic activation^[2]. In Vivo: Amprenavir is able to promote regression of hepatocarcinoma growth in vivo by anti-angiogenetic and overall anti-tumor activities, independently by PI3K/AKT related pathways that at today is one of the more suggestive hypothesis to explain the anti-tumor effects of the different protease inhibitors^[2]. Amprenavir efficiently activates PXR and induces PXR target gene expression in vitro and in vivo. Short-term exposure to amprenavirsignificantly increases plasma total cholesterol and atherogenic low-density lipoprotein cholesterol levels in wild-type mice, but not in PXR-deficient mice^[3].