Affinity-based protein profiling has proven to be a powerful method in target identification of bioactive molecules. Here, this technology was applied in two photoreactive anticancer inhibitors, arenobufagin and HM30181. Using UV irradiation, these photoreactive reagents can covalently cross-link to target proteins, leading to a covalent binding with target proteins. Moreover, the cellular on/off targets of these two molecules, including ATP1A1, MDR1, PARP1, DDX5, NOP2, RAB6A, and ERGIC1 were first identified by affinity-based protein profiling and bioimaging approaches. The protein hit, PARP1, was further validated to be involved in the function of the anticancer effects.

中文翻译：

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基于亲和力的蛋白质谱分析揭示了光反应性抗癌抑制剂的细胞靶标。

基于亲和力的蛋白质谱分析已被证明是生物活性分子靶标鉴定的有力方法。在这里，这项技术被应用于两种光反应性抗癌抑制剂，槟榔蟾蜍精和HM30181。使用紫外线照射，这些光反应试剂可以与目标蛋白共价交联，从而导致与目标蛋白的共价结合。此外，这两个分子的细胞开/关靶标，包括ATP1A1，MDR1，PARP1，DDX5，NOP2，RAB6A和ERGIC1，首先是通过基于亲和力的蛋白质谱分析和生物成像方法鉴定的。进一步验证了蛋白命中的PARP1参与了抗癌作用的功能。