Macrocyclic bisindolylmaleimides as inhibitors of protein kinase C and glycogen synthase kinase-3.

Article Details

Citation

Zhang HC, White KB, Ye H, McComsey DF, Derian CK, Addo MF, Andrade-Gordon P, Eckardt AJ, Conway BR, Westover L, Xu JZ, Look R, Demarest KT, Emanuel S, Maryanoff BE

Macrocyclic bisindolylmaleimides as inhibitors of protein kinase C and glycogen synthase kinase-3.

Bioorg Med Chem Lett. 2003 Sep 15;13(18):3049-53.

PubMed ID
12941331 [ View in PubMed
]
Abstract

Efficient methods were developed to synthesize a novel series of macrocyclic bisindolylmaleimides containing linkers with multiple heteroatoms. Potent inhibitors (single digit nanomolar IC(50)) for PKC-beta and GSK-3beta were identified, and compounds showed good selectivity over PKC-alpha, -gamma, -delta, -epsilon, and -zeta. Representative compound 5a also had high selectivity in a screening panel of 10 other protein kinases. In cell-based functional assays, several compounds effectively blocked interleukin-8 release induced by PKC-betaII and increased glycogen synthase activity by inhibiting GSK-3beta.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
StaurosporineGlycogen synthase kinase-3 betaIC 50 (nM)89N/AN/ADetails