Beyond the MEK-pocket: can current MEK kinase inhibitors be utilized to synthesize novel type III NCKIs? Does the MEK-pocket exist in kinases other than MEK?

Haile Tecle; Jianxing Shao; Yanhong Li; Michael Kothe; Steven Kazmirski; Julie Penzotti; Yuan-Hua Ding; Jeffrey Ohren; Deb Moshinsky; Rocco Coli; Nidhi Jhawar; Emilia Bora; Suzanne Jacques-O'Hagan; Joe Wu

doi:10.1016/j.bmcl.2008.10.108

Beyond the MEK-pocket: can current MEK kinase inhibitors be utilized to synthesize novel type III NCKIs? Does the MEK-pocket exist in kinases other than MEK?

Bioorg Med Chem Lett. 2009 Jan 1;19(1):226-9. doi: 10.1016/j.bmcl.2008.10.108. Epub 2008 Oct 31.

Authors

Haile Tecle¹, Jianxing Shao, Yanhong Li, Michael Kothe, Steven Kazmirski, Julie Penzotti, Yuan-Hua Ding, Jeffrey Ohren, Deb Moshinsky, Rocco Coli, Nidhi Jhawar, Emilia Bora, Suzanne Jacques-O'Hagan, Joe Wu

Affiliation

¹ Pfizer Global Research and Development, Research Technology Center, Cambridge, MA 02139, USA. haile.tecle@pfizer.com

PMID: 19019675
DOI: 10.1016/j.bmcl.2008.10.108

Abstract

An approach and preliminary results for utilizing legacy MEK inhibitors as templates for a reiterative structural based design and synthesis of novel, type III NCKIs (non-classical kinase inhibitors) is described. Evidence is provided that the MEK-pocket or pockets closely related to it may exist in kinases other than MEK.

MeSH terms

Catalytic Domain
Drug Design
Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors*
Protein Kinase Inhibitors / chemical synthesis*
Protein Kinase Inhibitors / chemistry
Protein Kinase Inhibitors / pharmacology

Substances

Protein Kinase Inhibitors
Mitogen-Activated Protein Kinase Kinases