Department of Biochemistry and Microbiology, University of Chemistry and Technology Prague, Technická 5, 166 28, Prague 6, Czech Republic.
Faculty of Medicine in Pilsen, Charles University, Alej Svobody 76, 323 00 Pilsen, Czech Republic.
J Med Chem. 2020 Mar 12;63(5):1937-1963. doi: 10.1021/acs.jmedchem.9b01509. Epub 2020 Feb 17.
The sarco/endoplasmic reticulum calcium ATPase (SERCA), which plays a key role in the maintenance of Ca ion homeostasis, is an extensively studied enzyme, the inhibition of which has a considerable impact on cell life and death decision. To date, several SERCA inhibitors have been thoroughly studied and the most notable one, a derivative of the sesquiterpene lactone thapsigargin, is gradually approaching a clinical application. Meanwhile, new compounds with SERCA-inhibiting properties of natural, synthetic, or semisynthetic origin are being discovered and/or developed; some of these might also be suitable for the development of new drugs with improved performance. This review brings an up-to-date comprehensive overview of recently discovered compounds with the potential of SERCA inhibition, discusses their mechanism of action, and highlights their potential clinical applications, such as cancer treatment.
肌浆/内质网钙 ATP 酶（SERCA）在维持钙离子动态平衡中发挥着关键作用，是一种经过广泛研究的酶，其抑制作用对细胞的生死决策有重大影响。迄今为止，已经对几种 SERCA 抑制剂进行了深入研究，其中最著名的一种是倍半萜内酯 thapsigargin 的衍生物，它正在逐渐接近临床应用。与此同时，具有天然、合成或半合成来源的 SERCA 抑制特性的新化合物也在被发现和/或开发；其中一些化合物也可能适合开发具有更好性能的新药。本文综述了最近发现的具有 SERCA 抑制潜力的化合物，讨论了它们的作用机制，并强调了它们在癌症治疗等方面的潜在临床应用。
