{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["6(1)"],"submitter":["Johnson CN"],"pubmed_abstract":["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 of a low-nanomolar, cell-penetrant Type II inhibitor suitable for use as a chemical probe for MELK."],"journal":["ACS medicinal chemistry letters"],"pagination":["31-6"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4291807"],"repository":["biostudies-literature"],"pubmed_title":["Structure-Based Design of Type II Inhibitors Applied to Maternal Embryonic Leucine Zipper Kinase."],"pmcid":["PMC4291807"],"pubmed_authors":["Adelinet C","McMenamin R","Rees DC","Berdini V","Frederickson M","Freyne EJ","Beke L","Coyle JE","Day PJ","Meerpoel L","Brehmer D","Mevellec L","Howard S","Pasquier E","Linders JT","Gilissen RA","Patel S","Bonnet P","Calo F","Hamlett CC","Johnson CN"],"additional_accession":[]},"is_claimable":false,"name":"Structure-Based Design of Type II Inhibitors Applied to Maternal Embryonic Leucine Zipper Kinase.","description":"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 of a low-nanomolar, cell-penetrant Type II inhibitor suitable for use as a chemical probe for MELK.","dates":{"release":"2015-01-01T00:00:00Z","publication":"2015 Jan","modification":"2026-05-03T06:52:22.712Z","creation":"2019-03-27T01:43:19Z"},"accession":"S-EPMC4291807","cross_references":{"pubmed":["25589926"],"doi":["10.1021/ml5001273"]}}