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December 12, 2007 NEW YORK (Reuters Health) - A new Abl kinase inhibitor that eliminates resistance to nilotinib and dasatinib in the treatment of chronic myeloid leukemia (CML) in mice and in human cell lines was described this week at the 49th annual meeting of the American Society of Hematology in Atlanta, Georgia. "There is only a small recovery after the development of resistance in CML," principal investigator Dr. Michael Deininger of Oregon Health and Science University Cancer Institute in Portland told Reuters Health. The new drug, with the investigational name SGX70393 (SGX Pharmaceuticals), "is effective against the gatekeeper of resistance," he explained. SGX70393 is an azapyridine-based Abl kinase inhibitor. Bcr-Abl-3151, a mutation that prevents drug binding, is present in most patients with CML who relapse after treatment with the Bcr-Abl kinase inhibitors dasatinib or nilotinib. SGX70393 is effective against Bcr-Abl and Bcr-Abl-3151. "Remarkably," Dr. Deininger's group reported, "outgrowth of resistant clones is completely suppressed" in tumor cell lines treated with SGX70393 in combination with nilotinib or dasatinib. SGX70393 inhibited tumor growth driven by Bcr-Abl-1351 in mice, while imatinib had no effect. However, the researchers add, "as a broader spectrum of mutations accounts for imatinib resistance, patients with acquired dasatinib or nilotinib resistance may continue to harbor residual mutant clones other than T315I. Thus, the full clinical potential of SGX70393 may be realized in combinations with a second Abl kinase inhibitor." Dr. Deininger commented that, "when combined with the tyrosine kinase inhibitors, this drug can induce longer-lasting remissions and it could be used to treat patients with more aggressive strains of CML. It could also be used earlier in the course of treatment to prevent resistance from developing in the first place." SGX Pharmaceuticals plans to file an NDA in the second half of 2008. "Clinical trials are at least a year away," Dr. Deininger said. Copyright 2008 Reuters. Click for Restrictions.
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