Description: Fostemsavir (BMS-663068; BMS663068; Rukobia), the phosphonooxymethyl prodrug of BMS-626529, is an approved (in 2020) antiretroviral medication for adults living with HIV/AIDS. It is a novel attachment inhibitor that targets HIV-1 gp120 and prevents its binding to CD4+ T cells. The activity of BMS-626529 is virus dependent, due to heterogeneity within gp120. In order to better understand the anti-HIV-1 spectrum of BMS-626529 against HIV-1, in vitro activities against a wide variety of laboratory strains and clinical isolates were determined. BMS-626529 had half-maximal effective concentration (EC(50)) values of<10 nm='' against='' the='' vast='' majority='' of='' viral='' susceptibility='' varied='' by=''>6 log(10), with half-maximal effective concentration values in the low pM range against the most susceptible viruses. The in vitro antiviral activity of BMS-626529 was generally not associated with either tropism or subtype, with few exceptions. Measurement of the binding affinity of BMS-626529 for purified gp120 suggests that a contributory factor to its inhibitory potency may be a relatively long dissociative half-life. Finally, in two-drug combination studies, BMS-626529 demonstrated additive or synergistic interactions with antiretroviral drugs of different mechanistic classes. These results suggest that BMS-626529 should be active against the majority of HIV-1 viruses and support the continued clinical development of the compound.

References: Nowicka-Sans B, et al. In vitro antiviral characteristics of HIV-1 attachment inhibitor BMS-626529, the active component of the prodrug BMS-663068. Antimicrob Agents Chemother. 2012 Jul;56(7):3498-507.