| Literature DB >> 24138940 |
Colin H MacKinnon1, Kevin Lau, Jason D Burch, Yuan Chen, Jonathon Dines, Xiao Ding, Charles Eigenbrot, Alexander Heifetz, Allan Jaochico, Adam Johnson, Joachim Kraemer, Susanne Kruger, Thomas M Krülle, Marya Liimatta, Justin Ly, Rosemary Maghames, Christian A G N Montalbetti, Daniel F Ortwine, Yolanda Pérez-Fuertes, Steven Shia, Daniel B Stein, Giancarlo Trani, Darshan G Vaidya, Xiaolu Wang, Steven M Bromidge, Lawren C Wu, Zhonghua Pei.
Abstract
Inhibition of the non-receptor tyrosine kinase ITK, a component of the T-cell receptor signalling cascade, may represent a novel treatment for allergic asthma. Here we report the structure-based optimization of a series of benzothiazole amides that demonstrate sub-nanomolar inhibitory potency against ITK with good cellular activity and kinase selectivity. We also elucidate the binding mode of these inhibitors by solving the X-ray crystal structures of several inhibitor-ITK complexes.Entities:
Keywords: Anti-inflammatory; Asthma; Benzothiazole; ITK inhibitor; SAR; TCR signalling
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Year: 2013 PMID： 24138940 DOI： 10.1016/j.bmcl.2013.09.069
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823