Fragment-based discovery of type I inhibitors of maternal embryonic leucine zipper kinase.

ABSTRACT: Fragment-based drug design was successfully applied to maternal embryonic leucine zipper kinase (MELK). A low affinity (160 μM) fragment hit was identified, which bound to the hinge region with an atypical binding mode, and this was optimized using structure-based design into a low-nanomolar and cell-penetrant inhibitor, with a good selectivity profile, suitable for use as a chemical probe for elucidation of MELK biology.

SUBMITTER: Johnson CN 

PROVIDER: S-EPMC4291735 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature