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Structure‐Guided Design of a Highly Selective Glycogen Synthase Kinase‐3β Inhibitor: a Superior Neuroprotective Pyrazolone Showing Antimania Effects
Author(s) -
Chen Wenwen,
Gaisina Iri.,
Gunosewoyo Hendra,
Malekiani Sam A.,
Hanania Taleen,
Kozikowski Alan P.
Publication year - 2011
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201100231
Subject(s) - gsk 3 , gsk3b , staurosporine , kinase , neuroprotection , cyclin dependent kinase , glycogen synthase , biochemistry , chemistry , computational biology , enzyme , biology , pharmacology , gene , protein kinase a , cell cycle
A new craze! A new chemical scaffold, namely a staurosporine‐like molecule (shown) possessing a pyrazolone core, was found to be highly selective for glycogen synthase kinase 3 over a group of other homologous kinases, including typical cyclin‐dependent kinases. This compound gave an impressive dose–response curve for neuroprotection in the homocysteic acid model of oxidative stress (graph shown), and furthermore, blocked chemically induced mania‐like effects in mice.