GW433908G is a selective inhibitor of antiretroviral protease with the concentration of 1395 mg nM once daily in clinical trial [1].

Antiretroviral protease is a subfamily of protease inhibitors and plays a pivotal role in treating HIV/AIDS and HCV infection. It has been reported that drugs designed as protease inhibitors can prevent viral replication by selectively binding to viral proteases (e.g. HIV-1 protease) and blocking proteolytic cleavage of protein precursors that are necessary for the production of infectious viral particles [2] [3].

GW433908 is a potent antiretroviral protease inhibitor and has improved solubility than amprenavir capsules. Many clinical studies have been done to examine GE433908 safety and pharmacokinetic profiles. In healthy male volunteers, administered GW433908 as tablets or suspension, food had slight effect on its pharmacokinetics and with fewer tablets GW433908 were well tolerated and delivered plasma amprenavir concentrations equivalent to the recommended therapeutic amprenavir dose which may be of clinical benefit in the treatment of HIV infection [4]. As a phosphate ester prodrug of the antiretroviral protease inhibitor amprenavir, GW433908 (1395 mg, QD) combined with efavirenz (200 mg, QD) decreased plasma APV exposure when tested with healthy volunteers [1].

References:
[1]. Wire, M.B., et al., Pharmacokinetics and safety of GW433908 and ritonavir, with and without efavirenz, in healthy volunteers. Aids, 2004. 18(6): p. 897-907.
[2]. Hamada, Y., et al., High incidence of renal stones among HIV-infected patients on ritonavir-boosted atazanavir than in those receiving other protease inhibitor-containing antiretroviral therapy. Clin Infect Dis, 2012. 55(9): p. 1262-9.
[3]. Zheng, Y., et al., Antiretroviral therapy and efficacy after virologic failure on first-line boosted protease inhibitor regimens. Clin Infect Dis, 2014. 59(6): p. 888-96.
[4]. Falcoz, C., et al., Pharmacokinetics of GW433908, a prodrug of amprenavir, in healthy male volunteers. J Clin Pharmacol, 2002. 42(8): p. 887-98.