Discovery of a potent and selective c-Kit inhibitor for the treatment of inflammatory diseases

Ning Chen; Roland W Bürli; Susana Neira; Randall Hungate; Dawei Zhang; Violeta Yu; Yen Nguyen; Yanyan Tudor; Matthew Plant; Shaun Flynn; Kristin L Meagher; Matthew R Lee; Xuxia Zhang; Andrea Itano; Michael Schrag; Yang Xu; Gordon Y Ng; Essa Hu

doi:10.1016/j.bmcl.2008.05.089

Discovery of a potent and selective c-Kit inhibitor for the treatment of inflammatory diseases

Bioorg Med Chem Lett. 2008 Jul 15;18(14):4137-41. doi: 10.1016/j.bmcl.2008.05.089. Epub 2008 May 28.

Authors

Ning Chen¹, Roland W Bürli, Susana Neira, Randall Hungate, Dawei Zhang, Violeta Yu, Yen Nguyen, Yanyan Tudor, Matthew Plant, Shaun Flynn, Kristin L Meagher, Matthew R Lee, Xuxia Zhang, Andrea Itano, Michael Schrag, Yang Xu, Gordon Y Ng, Essa Hu

Affiliation

¹ Department of Medicinal Chemistry, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA. chenc@amgen.com

PMID: 18554909
DOI: 10.1016/j.bmcl.2008.05.089

Abstract

A potent and selective c-Kit inhibitor 20 was identified through a structure-activity relationship study. In an in vivo mouse model of mast cell activation, 20 blocked the SCF-induced histamine release with an EC(50) of 26 nM.

MeSH terms

Animals
Chemistry, Pharmaceutical / methods*
Drug Design
Histamine Release / drug effects
Inflammation / drug therapy*
Inhibitory Concentration 50
Kinetics
MAP Kinase Signaling System
Mast Cells / metabolism
Mice
Protein Kinase Inhibitors / chemical synthesis*
Protein Kinase Inhibitors / pharmacology*
Proto-Oncogene Proteins c-kit / chemistry*
Rats
Stem Cell Factor / metabolism
Structure-Activity Relationship

Substances

Protein Kinase Inhibitors
Stem Cell Factor
Proto-Oncogene Proteins c-kit