2. Academic Validation
  3. In vitro antiviral characteristics of HIV-1 attachment inhibitor BMS-626529, the active component of the prodrug BMS-663068

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. doi: 10.1128/AAC.00426-12.
Beata Nowicka-Sans 1,  Yi-Fei Gong,  Brian McAuliffe,  Ira Dicker,  Hsu-Tso Ho,  Nannan Zhou,  Betsy Eggers,  Pin-Fang Lin,  Neelanjana Ray,  Megan Wind-Rotolo,  Li Zhu,  Antara Majumdar,  David Stock,  Max Lataillade,  George J Hanna,  John D Matiskella,  Yasutsugu Ueda,  Tao Wang,  John F Kadow,  Nicholas A Meanwell,  Mark Krystal
Affiliations

Affiliation

  • 1 Bristol-Myers Squibb, Research and Development, Wallingford, Connecticut, USA.
PMID: 22547625 DOI: 10.1128/AAC.00426-12
Abstract

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. 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 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. 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.

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