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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.
Bioorganic & medicinal chemistry letters, 06/2017, Letnik: 27, Številka: 12Journal Article
Display omitted 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 17nM, 23nM, 25nM, and 8nM 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.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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