Potent inhibition of checkpoint kinase activity by a hymenialdisine-derived indoloazepine

Vasudha Sharma; Jetze J Tepe

doi:10.1016/j.bmcl.2004.05.079

Potent inhibition of checkpoint kinase activity by a hymenialdisine-derived indoloazepine

Bioorg Med Chem Lett. 2004 Aug 16;14(16):4319-21. doi: 10.1016/j.bmcl.2004.05.079.

Authors

Vasudha Sharma¹, Jetze J Tepe

Affiliation

¹ Department of Chemistry, Michigan State University, East Lansing, MI 48824, USA.

PMID: 15261294
DOI: 10.1016/j.bmcl.2004.05.079

Abstract

The marine sponge metabolite hymenialdisine is a potent inhibitor of a variety of kinases including MEK-1, GSK-3 beta, and CK1. In addition, hymenialdisine and debromohymenialdisine exhibit inhibition of the G(2) cell cycle checkpoint at micromolar concentrations. We report herein the potent inhibition of cell cycle kinase Chk2 by the indolic-hymenialdisine indoloazepine 1 (IC(50)=8 nM).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Azepines / chemistry*
Azepines / pharmacology*
Checkpoint Kinase 2
Enzyme Inhibitors / pharmacology*
Protein Serine-Threonine Kinases / antagonists & inhibitors*
Pyrroles / chemistry*

Substances

Azepines
Enzyme Inhibitors
Pyrroles
hymenialdisine
Checkpoint Kinase 2
Protein Serine-Threonine Kinases