Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1373464 | Bioorganic & Medicinal Chemistry Letters | 2007 | 6 Pages |
Virtual screening against a pCDK2/cyclin A crystal structure led to the identification of a potent and novel CDK2 inhibitor, which exhibited an unusual mode of interaction with the kinase binding motif. With the aid of X-ray crystallography and modelling, a medicinal chemistry strategy was implemented to probe the interactions seen in the crystal structure and to establish SAR. A fragment-based approach was also considered but a different, more conventional, binding mode was observed. Compound selectivity against GSK-3β was improved using a rational design strategy, with crystallographic verification of the CDK2 binding mode.
Graphical abstractVirtual screening identified a potent CDK2 inhibitor with a novel binding mode.Figure optionsDownload full-size imageDownload as PowerPoint slide