- 3-(7-Azaindolyl)-4-arylmaleimides as potent, selective inhibitors of glycogen synthase kinase-3.
3-(7-Azaindolyl)-4-arylmaleimides as potent, selective inhibitors of glycogen synthase kinase-3.
Bioorganic & medicinal chemistry letters (2004-05-20)
Han-Cheng Zhang, Hong Ye, Bruce R Conway, Claudia K Derian, Michael F Addo, Gee-Hong Kuo, Leonard R Hecker, Diane R Croll, Jian Li, Lori Westover, Jun Z Xu, Richard Look, Keith T Demarest, Patricia Andrade-Gordon, Bruce P Damiano, Bruce E Maryanoff
PMID15149684
RESUMEN
A novel series of acyclic 3-(7-azaindolyl)-4-(aryl/heteroaryl)maleimides was synthesized and evaluated for activity against GSK-3beta and selectivity versus PKC-betaII, as well as a broad panel of protein kinases. Compounds 14 and 17c potently inhibited GSK-3beta (IC(50)=7 and 26 nM, respectively) and exhibited excellent selectivity over PKC-betaII (325 and >385-fold, respectively). Compound 17c was also highly selective against 68 other protein kinases. In a cell-based functional assay, both 14 and 17c effectively increased glycogen synthase activity by inhibiting GSK-3beta.
MATERIALES
Referencia del producto
Marca
Descripción del producto