BMS-663068 is the phosphonooxymethyl prodrug of BMS-626529, a novel small-molecule 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.?BMS-626529 had half-maximal effective concentration (EC(50)) values of <10 nM against the vast majority of viral isolates;?however, 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.?