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ID: ALA5236671
Journal: Bioorg Med Chem Lett
Title: Synthesis and biological evaluation of novel aromatic amide derivatives as potential BCR-ABL inhibitors.
Authors: Wang X, Xu Z, Feng J, Pan G, He X, Lv M, Chen H, Jiang W, Ji J, Yang M.
Abstract: BCR-ABL1 kinase is a key driver of the pathophysiology of chronic myeloid leukemia (CML). Current treatments need to broaden the chemical diversity of BCR-ABL1 kinase inhibitors to overcome drug resistance. We designed and synthesized a series of aromatic amide derivatives based on several generations of BCR-ABL1 kinase inhibitors. Biological studies showed that compared with Imatinib, these compounds showed significant proliferation inhibitory activities of HL-60 and K562 in cell activity assay. Compounds 4g and 4j exhibited significant anti-tumor activity against the K562 cells with IC50 values of 6.03 ± 0.49 μM and 5.66 ± 2.06 μM respectively. Compounds 4g and 4j, as potential BCR-ABL1 inhibitors, inhibit the phosphorylation of ABL1 and CRKL in a dose-dependent manner. Therefore, compounds 4g and 4j can be used as a starting point for further optimization.
CiteXplore: 36681201