Background:

EC50<10 nM against the vast majority of viral isolates

HIV-1 attachment inhibitors represent a new class of entry inhibitors that prevent the initial interaction between virus and host cell by binding to the viral envelope protein gp120 and blocking attachment of the virus to the CD4 receptor on CD4+ T-cells. BMS-626529 is a novel small-molecule attachment inhibitor that targets HIV-1 gp120 and prevents its binding to CD4+ T-cells.

In vitro: The activity of BMS-626529 is virus dependent, due to heterogeneity within gp120. BMS-626529 had half-maximal effective concentration values of<10 nm against the vast majority of viral isolates; however, susceptibility varied by>6 log10, with half-maximal effective concentration values in the low pM range against the most susceptible viruses. 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 [1].

In vivo: No animal in-vivo data available currently

Clinical trial: BMS-663068 is a prodrug of the small-molecule inhibitor BMS-626529. The maximum median decreased in plasma HIV-1 RNA load from baseline ranged from 1.21 to 1.73 log10 copies/mL. Plasma concentrations of BMS-626529 were not associated with an antiviral response, while low baseline inhibitory concentrations and the minimum and average steady-state BMS-626529 plasma concentrations, when adjusted by the baseline protein binding–adjusted 90% inhibitory concentration, were linked with antiviral response. BMS-663068 was generally well tolerated [2].

参考文献:
[1] Nowicka-Sans B, Gong YF, McAuliffe B, Dicker I, Ho HT, Zhou N, Eggers B, Lin PF, Ray N, Wind-Rotolo M, Zhu L, Majumdar A, Stock D, Lataillade M, Hanna GJ, Matiskella JD, Ueda Y, Wang T, Kadow JF, Meanwell NA, Krystal M.  In vitro antiviral characteristics of HIV-1 attachment inhibitor BMS-626529, the active component of the prodrug BMS-663068. Antimicrob Agents Chemother. 2012;56(7):3498-507.
[2] Nettles RE, Schürmann D, Zhu L, Stonier M, Huang SP, Chang I, Chien C, Krystal M, Wind-Rotolo M, Ray N, Hanna GJ, Bertz R, Grasela D.  Pharmacodynamics, safety, and pharmacokinetics of BMS-663068, an oral HIV-1 attachment inhibitor in HIV-1-infected subjects. J Infect Dis. 2012;206(7):1002-11.