Ontology highlight
ABSTRACT:
SUBMITTER: Johnson CN
PROVIDER: S-EPMC4291807 | biostudies-other | 2015 Jan
REPOSITORIES: biostudies-other
Johnson Christopher N CN Adelinet Christophe C Berdini Valerio V Beke Lijs L Bonnet Pascal P Brehmer Dirk D Calo Frederick F 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 Mevellec Laurence L McMenamin Rachel R Pasquier Elisabeth E Patel Sahil S Rees David C DC Linders Joannes T M JT
ACS medicinal chemistry letters 20140523 1
A novel Type II kinase inhibitor chemotype has been identified for maternal embryonic leucine zipper kinase (MELK) using structure-based ligand design. The strategy involved structural characterization of an induced DFG-out pocket by protein-ligand X-ray crystallography and incorporation of a slender linkage capable of bypassing a large gate-keeper residue, thus enabling design of molecules accessing both hinge and induced pocket regions. Optimization of an initial hit led to the identification ...[more]