Design, synthesis and biological evaluation of new bivalent quinazoline analogues as IAP antagonists.
Bioorg Med Chem Lett
; 34: 127676, 2021 02 15.
Article
en En
| MEDLINE
| ID: mdl-33166687
ABSTRACT
We recently reported the biological evaluations of monovalent IAP antagonist 7 with good potency (MDA-MB-231, IC50 = 19 nM). In an effort to increase cellular activity and improve favorable drug-like properties, we newly designed and synthesized bivalent analogues based on quinazoline structure of 7. Optimization of cellular potency and CYP inhibition led to the identification of 27, which showed dramatic increase of over 100-fold (IC50 = 0.14 nM) and caused substantial tumor regressions in MDA-MB-231 xenograft model. These results strongly support 27 as a promising bivalent antagonist for the development of an effective anti-tumor approaches.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Quinazolinas
/
Diseño de Fármacos
/
Proteínas Inhibidoras de la Apoptosis
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Antineoplásicos
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2021
Tipo del documento:
Article