1 research outputs found
Fragment-Based Discovery of Type I Inhibitors of Maternal Embryonic Leucine Zipper Kinase
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