Fragment-based discovery of type I inhibitors of maternal embryonic leucine zipper kinase.
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ABSTRACT:
SUBMITTER: Johnson CN
PROVIDER: S-EPMC4291735 | biostudies-literature | 2015 Jan
REPOSITORIES: biostudies-literature
Publications
Fragment-based discovery of type I inhibitors of maternal embryonic leucine zipper kinase.
Johnson Christopher N CN Berdini Valerio V Beke Lijs L Bonnet Pascal P Brehmer Dirk D Coyle Joseph E JE Day Phillip J PJ Frederickson Martyn M Freyne Eddy J E EJ Gilissen Ron A H J RA Hamlett Christopher C F CC Howard Steven S Meerpoel Lieven L McMenamin Rachel R Patel Sahil S Rees David C DC Sharff Andrew A Sommen François F Wu Tongfei T Linders Joannes T M JT
ACS medicinal chemistry letters 20140523 1
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. ...[more]
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