Fragment-based Discovery of Type I Inhibitors of Maternal Embryonic Leucine Zipper Kinase

Overview

Journal ACS Med Chem Lett

Publisher American Chemical Society

Specialty Chemistry

Date 2015 Jan 16

PMID 25589925

Citations 13

Authors

Christopher N Johnson

Valerio Berdini

Lijs Beke

Pascal Bonnet

Dirk Brehmer

Joseph E Coyle

Phillip J Day

Martyn Frederickson

Eddy J E Freyne

Ron A H J Gilissen

Christopher C F Hamlett

Steven Howard

Lieven Meerpoel

Rachel McMenamin

Sahil Patel

David C Rees

Andrew Sharff

Francois Sommen

Tongfei Wu

Joannes T M Linders

Affiliations

Soon will be listed here.

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.

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