An organometallic inhibitor for glycogen synthase kinase 3.
Replacing natural products with kinetically inert metal complexes may lead to a new class of therapeutics in which a metal center plays the role of an innocent bystander, organizing the orientation of the organic ligands in the receptor space. As an example of this approach, a ruthenium complex is described that copies the binding mode of indolocarbazole protein kinase inhibitors and serves as a reversible, low-nanomolar inhibitor for glycogen synthase kinase 3 (GSK-3).
Bregman
Howard
H
Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania 19104, USA.
Williams
Douglas S
DS
Atilla
G Ekin
GE
Carroll
Patrick J
PJ
Meggers
Eric
E
D002227:Carbazoles / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology; D007700:Kinetics; D008958:Models, Molecular; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D012428:Ruthenium / Q000737:chemistry / Q000494:pharmacology*
D002227:Carbazoles; D007211:Indoles; D009942:Organometallic Compounds; D047428:Protein Kinase Inhibitors; D012428:Ruthenium; D038362:Glycogen Synthase Kinase 3