School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-Sen University, Shenzhen 518107, P.R. China.
Curr Med Chem. 2024;31(20):2955-2973. doi: 10.2174/0929867331666230714144851.
Metabolic reprogramming of cells, from the normal mode of glucose metabolism named glycolysis, is a pivotal characteristic of impending cancerous cells. Pyruvate kinase M2 (PKM2), an important enzyme that catalyzes the final rate-limiting stage during glycolysis, is highly expressed in numerous types of tumors and aids in development of favorable conditions for the survival of tumor cells. Increasing evidence has suggested that PKM2 is one of promising targets for innovative drug discovery, especially for the developments of antitumor therapeutics. Herein, we systematically summarize the recent advancement on PKM2 modulators including inhibitors and activators in cancer applications. We also discussed the classifications of pyruvate kinases in mammals and the biological functions of PKM2 in this review. We do hope that this review would provide a comprehensive understanding of the current research on PKM2 modulators, which may benefit the development of more potent PKM2-related drug candidates to treat PKM2-associated diseases including cancers in future.
细胞的代谢重编程，从葡萄糖代谢的正常模式即糖酵解，是即将发生癌变的细胞的一个关键特征。丙酮酸激酶 M2（PKM2）是一种重要的酶，它在糖酵解的最后限速阶段起催化作用，在许多类型的肿瘤中高表达，并有助于为肿瘤细胞的生存创造有利条件。越来越多的证据表明，PKM2 是创新药物发现的有前途的靶点之一，特别是在抗肿瘤治疗药物的开发方面。本文系统地总结了 PKM2 调节剂（包括抑制剂和激活剂）在癌症应用中的最新进展。我们还讨论了哺乳动物中丙酮酸激酶的分类以及 PKM2 的生物学功能。我们希望本综述能全面了解 PKM2 调节剂的当前研究，这可能有助于未来开发更有效的与 PKM2 相关的药物候选物来治疗与 PKM2 相关的疾病，包括癌症。
