1422355-80-3Relevant academic research and scientific papers
Discovery of a novel and potent class of anti-HIV-1 maturation inhibitors with improved virology profile against gag polymorphisms
Tang, Jun,Jones, Stacey A.,Jeffrey, Jerry L.,Miranda, Sonia R.,Galardi, Cristin M.,Irlbeck, David M.,Brown, Kevin W.,McDanal, Charlene B.,Johns, Brian A.
, p. 2689 - 2694 (2017/05/29)
A new class of betulin-derived α-keto amides was identified as HIV-1 maturation inhibitors. Through lead optimization, GSK8999 was identified with IC50 values of 17?nM, 23?nM, 25?nM, and 8?nM for wild type, Q369H, V370A, and T371A respectively. When tested in a panel of 62 HIV-1 isolates covering a diversity of CA-SP1 genotypes including A, AE, B, C, and G using a PBMC based assay, GSK8999 was potent against 57 of 62 isolates demonstrating an improvement over the first generation maturation inhibitor BVM. The data disclosed here also demonstrated that the new α-keto amide GSK8999 has a mechanism of action consistent with inhibition of the proteolytic cleavage of CA-SP1.
