Structural basis for substrate binding selectivity to the anti-apoptotic Bcl-2 family proteins

来源 :2012长三角药物化学研讨会 | 被引量 : 0次 | 上传用户:zxh0532
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  Anti-apoptotic Bcl-2 family proteins (e.g.Bcl-2, Bcl-xl, Mcl-1) are promising targets for anticancer drug design[1].ABT-737, a selective potent inhibitor of anti-apoptotic bcl-2 proteins, becomes a poor killer of tumor cells in which Mcl-1 is over-expressed.A rational explanation is that it possess a high affinity with Bcl-2, Bcl-xl, Bcl-w, but fails to engage Mcl-1 or A1 [2].Due to the importance of Mcl-1 in cancer [3], designing broad-spectrum small-molecule inhibitors targeting Bcl-xl,Bcl-2 and Mcl-1 may be a ideal strategy for cancer therapy.
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