Linked Life Data

19707322

Source:http://linkedlifedata.com/resource/pubmed/id/19707322

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pubmed-article:19707322pubmed:abstractTextAlthough high rates of complete hematologic and cytogenetic remission have been observed in patients with chronic phase chronic myeloid leukemia (CML) treated with imatinib, a short duration of response with eventual emergence of imatinib resistance has also been reported in a subset of CML patients. The most frequent clinically relevant mechanisms that change imatinib sensitivity in BCR-ABL-transformed cells are mutations within the Abl kinase domain, affecting several of its properties. Crystal structure analysis of the Abl-imatinib complex has proven helpful in identifying potential critical residues that hinder interactions of imatinib with mutated Abl. This has led to the development of a second generation of targeted therapies such as nilotinib and dasatinib, already in phase II clinical trials or SKI-606 and MK-0457 in phase I trials. In this review, we discuss the activity of nilotinib, developed by Novartis using a rational drug design strategy in which imatinib served as the lead compound. Preliminary studies demonstrated that nilotinib has more efficacy than imatinib in inhibiting proliferation of BCR-ABL-dependent cells, a relatively safety profile and clinical efficacy in all phases of CML.lld:pubmed
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pubmed-article:19707322pubmed:authorpubmed-author:BaccaraniMich...lld:pubmed
pubmed-article:19707322pubmed:authorpubmed-author:MartinelliGio...lld:pubmed
pubmed-article:19707322pubmed:authorpubmed-author:RostiGiananto...lld:pubmed
pubmed-article:19707322pubmed:authorpubmed-author:SoveriniSimon...lld:pubmed
pubmed-article:19707322pubmed:authorpubmed-author:PalandriFranc...lld:pubmed
pubmed-article:19707322pubmed:authorpubmed-author:CastagnettiFa...lld:pubmed
pubmed-article:19707322pubmed:authorpubmed-author:IacobucciIlar...lld:pubmed
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pubmed-article:19707322pubmed:pagination121-7lld:pubmed
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pubmed-article:19707322pubmed:articleTitleNilotinib: a novel encouraging therapeutic option for chronic myeloid leukemia patients with imatinib resistance or intolerance.lld:pubmed
pubmed-article:19707322pubmed:affiliationInstitute of Hematology and Medical Oncology "Seràgnoli", University of Bologna, Bologna, Italy.lld:pubmed
pubmed-article:19707322pubmed:publicationTypeJournal Articlelld:pubmed