Beneficial effects of combining a type II ATP competitive inhibitor with an allosteric competitive inhibitor of BCR-ABL for the treatment of imatinib-sensitive and imatinib-resistant CML
نویسندگان
چکیده
منابع مشابه
Inhibitors of the Abl kinase directed at either the ATP- or myristate-binding site.
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....
متن کاملBeneficial effects of combining nilotinib and imatinib in preclinical models of BCR-ABL+ leukemias.
Drug resistance resulting from emergence of imatinib-resistant BCR-ABL point mutations is a significant problem in advanced-stage chronic myelogenous leukemia (CML). The BCR-ABL inhibitor, nilotinib (AMN107), is significantly more potent against BCR-ABL than imatinib, and is active against many imatinib-resistant BCR-ABL mutants. Phase 1/2 clinical trials show that nilotinib can induce remissio...
متن کاملthe investigation of the relationship between type a and type b personalities and quality of translation
چکیده ندارد.
Beneficial Effects of Combining Nilotinib and Imatinib in Preclinical Models of BCR/ABL+ Leukemias Nilotinib and Imatinib Against Bcr-Abl+ Leukemia
Grant Support: J.D.G is supported by NIH grant CA66996, and a Specialized Center of Research Award from the Leukemia and Lymphoma Society. J.D.G. is also supported by NIH grants CA36167 and DK50654. P.W.M., J.M., and D.F. are employees of Novartis Pharma AG, Basel, Switzerland. J.D.G. has a financial interest with Novartis Pharma AG. Blood First Edition Paper, prepublished online October 26, 20...
متن کاملDiscovery of allosteric BCR-ABL inhibitors from phenotypic screen to clinical candidate.
The development of imatinib, an ATP-competitive inhibitor of the BCR-ABL oncoprotein, has revolutionized the treatment of chronic myelogenous leukemia (CML). Unfortunately, the leukemia eventually becomes resistant imatinib as a result of emergence of cells expressing drug insensitive BCR-ABL mutant proteins. This has motivated the development of several next-generation ATP-competitive drugs. T...
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ژورنال
عنوان ژورنال: Leukemia
سال: 2010
ISSN: 0887-6924,1476-5551
DOI: 10.1038/leu.2010.107