Discovery of a novel and potent class of anti-HIV-1 maturation inhibitors with improved virology profile against gag polymorphisms.
Bioorg Med Chem Lett
; 27(12): 2689-2694, 2017 06 15.
Article
em En
| MEDLINE
| ID: mdl-28454672
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Polimorfismo Genético
/
Triterpenos
/
HIV-1
/
Fármacos Anti-HIV
/
Produtos do Gene gag do Vírus da Imunodeficiência Humana
/
Descoberta de Drogas
/
Amidas
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article