| Literature DB >> 15710326 |
Ellen Weisberg1, Paul W Manley, Werner Breitenstein, Josef Brüggen, Sandra W Cowan-Jacob, Arghya Ray, Brian Huntly, Doriano Fabbro, Gabriele Fendrich, Elizabeth Hall-Meyers, Andrew L Kung, Jürgen Mestan, George Q Daley, Linda Callahan, Laurie Catley, Cara Cavazza, Mohammad Azam, Azam Mohammed, Donna Neuberg, Renee D Wright, D Gary Gilliland, James D Griffin.
Abstract
The Bcr-Abl tyrosine kinase oncogene causes chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). We describe a novel selective inhibitor of Bcr-Abl, AMN107 (IC50 <30 nM), which is significantly more potent than imatinib, and active against a number of imatinib-resistant Bcr-Abl mutants. Crystallographic analysis of Abl-AMN107 complexes provides a structural explanation for the differential activity of AMN107 and imatinib against imatinib-resistant Bcr-Abl. Consistent with its in vitro and pharmacokinetic profile, AMN107 prolonged survival of mice injected with Bcr-Abl-transformed hematopoietic cell lines or primary marrow cells, and prolonged survival in imatinib-resistant CML mouse models. AMN107 is a promising new inhibitor for the therapy of CML and Ph+ ALL.Entities:
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Year: 2005 PMID： 15710326 DOI： 10.1016/j.ccr.2005.01.007
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743