Structure-Based Design of Type II Inhibitors Applied to Maternal Embryonic Leucine Zipper Kinase.
ACS Med Chem Lett
; 6(1): 31-6, 2015 Jan 08.
Article
en En
| MEDLINE
| ID: mdl-25589926
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.
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Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
ACS Med Chem Lett
Año:
2015
Tipo del documento:
Article
País de afiliación:
Reino Unido