p53: An Attractive Therapeutic Target for Cancer

doi:10.2174/1573406415666190621094704
摘要

癌症是世界范围内死亡的主要原因。当细胞周期调节基因由于环境和/或内部因素失去功能时，它就产生了。肿瘤抑制蛋白p53被称为基因组的守护者，在维持细胞基因组稳定性方面发挥着核心作用。超过50%的人类癌症中发现了TP53的突变，通常是由于负调控蛋白MDM2的过表达引起的。因此，通过阻断the murine double minute 2 (MDM2)与肿瘤抑制蛋白p53之间的蛋白-蛋白相互作用来重新激活p53已成为肿瘤学中最有前景的治疗策略。几种小分子已经被鉴定为有效的、选择性的和有效的p53-MDM2抑制剂。本文中，我们综述了p53-MDM2抑制剂的可给药性及其优化方法，以及按骨架类型分类的临床候选药物。
关键词: 癌症，肿瘤抑制蛋白p53，突变，p53-MDM2蛋白质相互作用，小分子抑制剂，p53重激活。
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ClinicalTrials.gov identifiers for MK-8242: NCT01463696
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ClinicalTrials.gov identifiers for CGM-097: NCT0176-
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ClinicalTrials.gov identifiers for DS-3032b: NCT0187-
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ClinicalTrials.gov identifiers for HDM201: NCT02780128
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DOI https://dx.doi.org/10.2174/1573406415666190621094704	Print ISSN 0929-8673
Publisher Name Bentham Science Publisher	Online ISSN 1875-533X
当代药物化学

p53:一个对癌症有吸引力的治疗靶点

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当代药物化学

p53:一个对癌症有吸引力的治疗靶点

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