TY - JOUR
T1 - GSK-3 inhibition
T2 - Achieving moderate efficacy with high selectivity
AU - Avrahami, Limor
AU - Licht-Murava, Avital
AU - Eisenstein, Miriam
AU - Eldar-Finkelman, Hagit
PY - 2013
Y1 - 2013
N2 - Inhibiting glycogen synthase kinase-3 (GSK-3) activity has become an attractive approach for treatment of neurodegenerative and psychiatric disorders. Diverse GSK-3 inhibitors have been reported and used in cellular and in vivo models. A major challenge, however, is achieving selectivity. In addition, it is increasingly recognized that a moderate inhibition of a cellular target, particularly for long-term treatment, provides more favorable outcome than complete inhibition. Substrate competitive inhibitors can fulfill the requirement for selectivity and allow fine tuning of the degree of inhibition. Here we describe the therapeutic potential of GSK-3 inhibitors and highlight our progress in the development of substrate competitive inhibitors. This article is part of a Special Issue entitled: Inhibitors of Protein Kinases (2012).
AB - Inhibiting glycogen synthase kinase-3 (GSK-3) activity has become an attractive approach for treatment of neurodegenerative and psychiatric disorders. Diverse GSK-3 inhibitors have been reported and used in cellular and in vivo models. A major challenge, however, is achieving selectivity. In addition, it is increasingly recognized that a moderate inhibition of a cellular target, particularly for long-term treatment, provides more favorable outcome than complete inhibition. Substrate competitive inhibitors can fulfill the requirement for selectivity and allow fine tuning of the degree of inhibition. Here we describe the therapeutic potential of GSK-3 inhibitors and highlight our progress in the development of substrate competitive inhibitors. This article is part of a Special Issue entitled: Inhibitors of Protein Kinases (2012).
KW - Alzheimer's disease
KW - CNS disorders
KW - Drug design
KW - GSK-3 inhibitors
KW - L803-mts
UR - http://www.scopus.com/inward/record.url?scp=84878874968&partnerID=8YFLogxK
U2 - 10.1016/j.bbapap.2013.01.016
DO - 10.1016/j.bbapap.2013.01.016
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.systematicreview???
AN - SCOPUS:84878874968
SN - 1570-9639
VL - 1834
SP - 1410
EP - 1414
JO - Biochimica et Biophysica Acta - Proteins and Proteomics
JF - Biochimica et Biophysica Acta - Proteins and Proteomics
IS - 7
ER -