Targeting Bcr–Abl by combining allosteric with ATP-binding-site inhibitors
نویسندگان
چکیده
منابع مشابه
Kinase selectivity potential for inhibitors targeting the ATP binding site: a network analysis
UNLABELLED MOTIVATION AND METHOD: Small-molecule inhibitors targeting the adenosine triphosphate (ATP) binding pocket of the catalytic domain of protein kinases have potential to become drugs devoid of (major) side effects, particularly if they bind selectively. Here, the sequences of the 518 human kinases are first mapped onto the structural alignment of 116 kinases of known three-dimensional ...
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Successful treatment of chronic myelogenous leukemia is based on inhibitors binding to the ATP site of the deregulated breakpoint cluster region (Bcr)-Abelson tyrosine kinase (Abl) fusion protein. Recently, a new type of allosteric inhibitors targeting the Abl myristoyl pocket was shown in preclinical studies to overcome ATP-site inhibitor resistance arising in some patients. Using NMR and smal...
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The ATP-competitive inhibitors dasatinib and nilotinib, which bind to catalytically different conformations of the Abl kinase domain, have recently been approved for the treatment of imatinib-resistant CML. These two new drugs, albeit very efficient against most of the imatinib-resistant mutants of Bcr-Abl, fail to effectively suppress the Bcr-Abl activity of the T315I (or gatekeeper) mutation....
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ژورنال
عنوان ژورنال: Nature
سال: 2010
ISSN: 0028-0836,1476-4687
DOI: 10.1038/nature08675