A new study by scientists at ARIAD provides an overview of the design of small molecule drugs to treat drug-resistant leukemia
ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) announced the publication for the first time, high-resolution structure of the protein responsible for the major clinically relevant genetic variants of drug-resistant chronic myeloid leukemia (CML). These findings by a team of scientists used for the design of ARIAD kinase inhibitors have been leadership ARIAD oral multi-target, AP24534, types of cancer for use in CML and others. The results were published in the September issue of Chemical Biology and Drug Design.ARIAD plans to file a new drug application for AP24534 in research later this year to begin clinical trials.CML is a slowly progressing cancer in which white blood cells are made in the bone marrow many. In most cases, a genetic abnormality involving the Bcr-Abl
protein, a tyrosine kinase encoded by the Philadelphia chromosome, the results of a constant growth of cancer cells active. Through studies of X-ray crystallography, this study showed in detail how inhibitors of the Bcr-Abl protein, such as AP24534, are able to overcome the structural changes induced by the T315I mutation and bind to the mutated form of the protein.The data show also explain why first-generation Bcr-Abl inhibitor imatinib, and the second generation of inhibitors of Bcr-Abl, including dasatinib and nilotinib, are not able to inhibit this key genetic variant and therefore are not against all effective forms of CML.In contrast to these first and second generation inhibitors of Bcr-Abl, AP24534 blocks all forms of potentially clinically relevant Bcr-Abl
protein, including the mutant protein (the target of imatinib), commonly mutated proteins (dasatinib and objectives nilotinib), and the T315I mutation of the protein. The mutation T315I Bcr-Abl currently 15 to 20 percent of all drug resistance in CML. The increased prevalence of T315I mutation, such as patients after treatment with the current second-generation inhibitors.There is a growing unmet medical need for new therapeutic
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