Fragment-based discovery of type I inhibitors of maternal embryonic leucine zipper kinase.
Basic Information
ID: ALA3352077
Journal: ACS Med Chem Lett
Title: Fragment-based discovery of type I inhibitors of maternal embryonic leucine zipper kinase.
Authors: Johnson CN, Berdini V, Beke L, Bonnet P, Brehmer D, Coyle JE, Day PJ, Frederickson M, Freyne EJ, Gilissen RA, Hamlett CC, Howard S, Meerpoel L, McMenamin R, Patel S, Rees DC, Sharff A, Sommen F, Wu T, Linders JT.
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.
CiteXplore: 25589925
DOI: 10.1021/ml5001245
Patent ID: ┄