A structure-activity relationship study of small-molecule inhibitors of GLI1-mediated transcription.
Biopolymers
; 95(1): 24-30, 2011 Jan.
Article
en En
| MEDLINE
| ID: mdl-20872873
ABSTRACT
We have previously reported ketoprofen amide compounds as inhibitors of GLI1-mediated transcription, an essential down-stream element of the Hedgehog (Hh) pathway. These compounds inhibited Gli-luciferase reporter in C3H10T1/2 cells that were exogenously transfected with GLI1 and in Rh30 cells that endogenously overexpress GLI1. Here we have designed new derivatives of these compounds aiming to explore the structure-activation relationship (SAR). By replacing the ketone carbonyl group of the ketoprofen moiety with an ether, amide, sulfonamide, or sulfone, we found several new compounds that are equipotent to the ketoprofen amide compounds. Among them, sulfone 30 inhibited Gli-luciferase reporter in C3H10T1/2 cells that were exogenously transfected with GLI1 and in Rh30 cells that endogenously overexpress GLI1.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
/
Biopolímeros
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Biopolymers
Año:
2011
Tipo del documento:
Article
País de afiliación:
Estados Unidos