| Literature DB >> 20338520 |
Wenjun Zhou1, Wooyoung Hur, Ultan McDermott, Amit Dutt, Wa Xian, Scott B Ficarro, Jianming Zhang, Sreenath V Sharma, Joan Brugge, Matthew Meyerson, Jeffrey Settleman, Nathanael S Gray.
Abstract
The fibroblast growth factor receptor tyrosine kinases (FGFR1, 2, 3, and 4) represent promising therapeutic targets in a number of cancers. We have developed the first potent and selective irreversible inhibitor of FGFR1, 2, 3, and 4, which we named FIIN-1 that forms a covalent bond with cysteine 486 located in the P loop of the FGFR1 ATP binding site. We demonstrated that the inhibitor potently inhibits Tel-FGFR1-transformed Ba/F3 cells (EC(50) = 14 nM) as well as numerous FGFR-dependent cancer cell lines. A biotin-derivatized version of the inhibitor, FIIN-1-biotin, was shown to covalently label FGFR1 at Cys486. FIIN-1 is a useful probe of FGFR-dependent cellular phenomena and may provide a starting point of the development of therapeutically relevant irreversible inhibitors of wild-type and drug-resistant forms of FGFR kinases. Copyright 2010 Elsevier Ltd. All rights reserved.Entities:
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Year: 2010 PMID： 20338520 PMCID： PMC2920453 DOI： 10.1016/j.chembiol.2010.02.007
Source DB: PubMed Journal: Chem Biol ISSN： 1074-5521