The role of structure and biophysics in the discovery of allosteric kinase inhibitors: ABL001, a potent and specific inhibitor of BCR-ABL
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چکیده
منابع مشابه
Cancer cocktails: ABL001 – hitting one target twice
Medicines [2] ABL001 is a small molecule designed to inhibit BCR-ABL, the same protein hit by imatinib and nilotinib, which are used to treat chronic myelogenous leukemia. But ABL001 has a different mechanism of action. It doesn’t bind the active site of its target. Instead it binds a different region of BCR-ABL, forcing a conformational change that disables the protein’s active site. According...
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Inhibition of Bcr-Abl kinase activity by imatinib for the treatment of chronic myeloid leukemia (CML) currently serves as the paradigm for targeting dominant oncogenes with small molecules. We recently reported the discovery of GNF-2 (1) and GNF-5 (2) as selective non-ATP competitive inhibitors of cellular Bcr-Abl kinase activity that target the myristate binding site. Here, we used cell-based ...
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تاریخ انتشار 2016