Rational design of potent GSK3beta inhibitors with selectivity for Cdk1 and Cdk2.
From an HTS hit, a series of potent and selective inhibitors of GSK3beta have been designed based on a Cdk2-homology model and with the help of several crystal structures of the compounds within Cdk2.
Lesuisse
Dominique
D
Medicinal Chemistry, 13 Quai Jules Guesde, 94300 Vitry-sur-Seine, France. dominique.lesuisse@sanofi-aventis.com
Dutruc-Rosset
Gilles
G
Tiraboschi
Gilles
G
Dreyer
Matthias K
MK
Maignan
Sébastien
S
Chevalier
Alain
A
Halley
Frank
F
Bertrand
Philippe
P
Burgevin
Marie-Claude
MC
Quarteronet
Dominique
D
Rooney
Thomas
T
D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors*; D051357:Cyclin-Dependent Kinase 2 / Q000037:antagonists & inhibitors*; D015195:Drug Design; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors*; D000071679:Glycogen Synthase Kinase 3 beta; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D013379:Substrate Specificity
D047428:Protein Kinase Inhibitors; D000071679:Glycogen Synthase Kinase 3 beta; D016203:CDC2 Protein Kinase; D051357:Cyclin-Dependent Kinase 2; D038362:Glycogen Synthase Kinase 3