Gilles Tiraboschi

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.

Design of potent and selective GSK3β inhibitors with acceptable safety profile and pharmacokinetics

From potent and selective inhibitors of GSK3beta displaying CYP1A2 inhibition and poor PK properties, mostly linked to metabolic instability and in vivo hydrolysis of the amide bond, we were able to obtain safe and orally available inhibitors with good half lives.