Peng Rujue, Zhan Yujie, Li Anqi, Lv Qiaoli, Xu Shan
School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, China.
Department of Oncology, Jiangxi Cancer Hospital, Nanchang 330029, China.
Bioorg Chem. 2024 Dec;153:107934. doi: 10.1016/j.bioorg.2024.107934. Epub 2024 Oct 28.
Phosphatidylinositol 3-kinases (PI3Ks) are widely expressed in tissues and cells throughout the body and are involved in a variety of physiological processes including cell growth and metabolism. The phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of the rapamycin (mTOR) signaling pathway (PI3K/AKT/mTOR, PAM) is a promising target for the treatment of many cancer types because it is significantly linked to tumorigenesis and development. Aberrant activation of this pathway is observed in the majority of tumors, particularly in breast cancer. The development of PI3K inhibitors has received much attention in recent years. PI3K inhibitors are effective drugs for the treatment of various types of malignant tumors. The FDA has approved a few PI3K inhibitors for commercialization, and the majority of PI3K inhibitors under clinical trials are expected to conquer cancers, including breast cancer. This article discusses the link between the PAM signaling system and breast cancer, as well as the current clinical applications of PAM pathway inhibitors in the treatment of breast cancer. This work summarizes and describes the development tactics of seven types of PI3K inhibitors targeting breast cancer, including morpholine-substituted thienopyrimidines, with the goal of informing future PI3K inhibitor research.
磷脂酰肌醇3激酶（PI3Ks）在全身组织和细胞中广泛表达，并参与包括细胞生长和代谢在内的多种生理过程。磷酸肌醇-3激酶（PI3K）/蛋白激酶B（AKT）/哺乳动物雷帕霉素靶蛋白（mTOR）信号通路（PI3K/AKT/mTOR，PAM）是治疗多种癌症类型的一个有前景的靶点，因为它与肿瘤发生和发展显著相关。在大多数肿瘤中，尤其是乳腺癌中，都观察到该通路的异常激活。近年来，PI3K抑制剂的研发备受关注。PI3K抑制剂是治疗各类恶性肿瘤的有效药物。美国食品药品监督管理局（FDA）已批准了几种PI3K抑制剂用于商业化，并且大多数处于临床试验阶段的PI3K抑制剂有望攻克包括乳腺癌在内的癌症。本文讨论了PAM信号系统与乳腺癌之间的联系，以及PAM通路抑制剂在乳腺癌治疗中的当前临床应用。这项工作总结并描述了七种靶向乳腺癌的PI3K抑制剂的研发策略，包括吗啉取代的噻吩并嘧啶，目的是为未来PI3K抑制剂的研究提供参考。
