Tongji School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Foundational Sciences, Central Michigan University College of Medicine, Mt. Pleasant, Michigan, USA.
Br J Pharmacol. 2019 Apr;176(7):817-831. doi: 10.1111/bph.14572. Epub 2019 Feb 28.
The transcription factor p53 is known as the guardian of the genome for its powerful anti-tumour capacity. However, mutations of p53 that undermine their protein structure, resulting in loss of tumour suppressor function and gain of oncogenic function, have been implicated in more than half of human cancers. The crucial role of mutant forms of p53 in cancer makes it an attractive therapeutic target. A large number of candidates, including low MW compounds, peptides, and nucleic acids, have been identified or designed to rescue p53 mutants and reactivate their anti-tumour capacity through a variety of mechanisms. In this review, we summarize the progress made in the reactivation of mutant forms of p53, focusing on the pharmacological mechanisms of the reactivators of p53 mutants.
转录因子 p53 因其强大的抗肿瘤能力而被称为基因组的守护者。然而,p53 突变破坏了其蛋白质结构,导致肿瘤抑制功能丧失和致癌功能获得,这与超过一半的人类癌症有关。突变型 p53 在癌症中的关键作用使其成为一个有吸引力的治疗靶点。已经鉴定或设计了大量候选物,包括低 MW 化合物、肽和核酸,以通过多种机制挽救 p53 突变体并重新激活其抗肿瘤能力。在这篇综述中,我们总结了突变型 p53 再激活的研究进展,重点介绍了 p53 突变体再激活剂的药理学机制。