Potent inhibition of checkpoint kinase activity by a hymenialdisine-derived indoloazepine.
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).
Sharma
Vasudha
V
Department of Chemistry, Michigan State University, East Lansing, MI 48824, USA.
Tepe
Jetze J
JJ
D001381:Azepines / Q000737:chemistry* / Q000494:pharmacology*; D064447:Checkpoint Kinase 2; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011758:Pyrroles / Q000737:chemistry*
D001381:Azepines; D004791:Enzyme Inhibitors; D011758:Pyrroles; C107079:hymenialdisine; D064447:Checkpoint Kinase 2; D017346:Protein Serine-Threonine Kinases