Amprenavir (agenerase)

Amprenavir (VX-478) is a HIV protease inhibitor(Ki=0.6 nM) used to treat HIV infection.

Amprenavir has an enzyme inhibition constant (Ki = 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 +/- 12.5 ng/mL (mean +/- SD) [1]. Amprenavir had direct inhibitory effects on invasion of Huh-7 hepatocarcinoma cell lines, inhibiting MMP proteolytic activation [2].

Amprenavir was 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 activated PXR and induced PXR target gene expression in vitro and in vivo. Short-term exposure to amprenavirsignificantly increased plasma total cholesterol and atherogenic low-density lipoprotein cholesterol levels in wild-type mice, but not in PXR-deficient mice [3]. Amprenavir has been approved for adults and children; the recommended capsule doses are 1200 mg twice daily for adults and 20 mg/kg twice daily or 15 mg/kg 3 times daily for children < 13 years of age or adolescents < 50 kg [1].

References:
[1]. Sadler BM, Stein DS. Clinical pharmacology and pharmacokinetics of amprenavir. Ann Pharmacother. 2002 Jan;36(1):102-18.
[2]. Esposito V, Verdina A, Manente L, Amprenavir inhibits the migration in human hepatocarcinoma cell and the growth of xenografts. J Cell Physiol. 2013 Mar;228(3):640-5.
[3]. Helsley RN, Sui Y, Ai N, Pregnane X Receptor Mediates Dyslipidemia Induced by the HIV Protease Inhibitor Amprenavir in Mice. Mol Pharmacol. 2013 Jun;83(6):1190-9.