Inside Cover: Probing an Allosteric Pocket of CDK2 with Small Molecules (ChemMedChem 1/2017). (5th January 2017)

• Record Type: Journal Article
• Authors: Christodoulou, Michael S.; Caporuscio, Fabiana; Restelli, Valentina; Carlino, Luca; Cannazza, Giuseppe; Costanzi, Elisa; Citti, Cinzia; Lo Presti, Leonardo; Pisani, Pasquale; Battistutta, Roberto; Broggini, Massimo; Passarella, Daniele; Rastelli, Giulio
• Is Part Of: ChemMedChem. Volume 12:Number 1(2017)
• Page Start: 2
• Page End: 2
• Publication Date: 2017-01-05
• Subjects: allosteric modulators -- computational chemistry -- cyclin-dependent kinase 2 -- protein kinases -- structure elucidation; Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.201600623
• Languages: English
• ISSNs: 1860-7179

Abstract

Abstract : The inside cover picture shows the first small‐molecule allosteric inhibitor of cyclin‐dependent kinase 2 (CDK2) binding within an allosteric pocket in the proximity of the αC helix and distinct from the ATP binding site. The target compound was fully characterized through chemical synthesis, X‐ray crystallography, modeling studies, and biological evaluations. It was able to inhibit the growth of different cancer cell lines as a racemic mixture and as pure enantiomers. More importantly, it allowed for the fine tuning of CDK2 activity and served as an excellent probe to study the allosteric modulation of the kinase, which is one of the most important targets interfering with cell cycle progression. More information can be found in the Full Paper by Giulio Rastelli et al. onpage 33 in Issue 1, 2017 (DOI:10.1002/cmdc.201600474 ).