Three optimized assays for the evaluation of compounds that can rescue p53 mutants

Drugs targeting p53 remain a proverbial Holy Grail of precision oncology, with over twenty compounds that can rescue p53 mutants reported so far. Here, we suggest three easily accessible assays to determine the thermostability, protein folding, and transcriptional activity of p53 mutants – the three go-to criteria for evaluating a rescue compound that acts by increasing p53 thermostability. Because of the diversity of p53 mutants, a compound that meets the criteria of one assay does not necessarily meet the criteria of the two other assays.
For complete details on the use and execution of these protocols, please refer to (Chen et al., 2021).

针对p53的药物一直是精准肿瘤学领域的传奇圣杯，截至目前已有超过二十种能够挽救p53突变体的化合物被报道。在此，我们提出了三种易于获取的检测方法，用于确定p53突变体的热稳定性、蛋白质折叠和转录活性——这三种标准是评估通过增加p53热稳定性起作用的挽救化合物的必备条件。鉴于p53突变体的多样性，一种满足某一检测方法标准的产品，未必能同时满足另外两种检测方法的条件。关于这些协议的使用和执行细节，请参阅（Chen等，2021年）。