Department of Neurology, Joint Research Institution of Altitude Health and Institute of Respiratory Health and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.
Department of Pharmacy, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, Sichuan, China.
J Med Chem. 2024 Jan 11;67(1):38-64. doi: 10.1021/acs.jmedchem.3c01802. Epub 2024 Jan 2.
Proviral integration sitea for Moloney-murine leukemia virus (PIM) kinases are a family of highly conserved serine/tyrosine kinases consisting of three members, PIM-1, PIM-2, and PIM-3. These kinases regulate a wide range of substrates through phosphorylation and affect key cellular processes such as transcription, translation, proliferation, apoptosis, and energy metabolism. Several PIM inhibitors are currently undergoing clinical trials, such as a phase I clinical trial of () for the treatment of relapsed diffuse large B-cell lymphoma that has been completed. The current focus encompasses the structural and biological characterization of PIM, ongoing research progress on small-molecule inhibitors undergoing clinical trials, and evaluation analysis of persisting challenges in this field. Additionally, the design and discovery of small-molecule inhibitors targeting PIM in recent years have been explored, with a particular emphasis on medicinal chemistry, aiming to provide valuable insights for the future development of PIM inhibitors.
前病毒整合位点 A 是莫洛尼鼠白血病病毒（PIM）激酶家族，由三个成员 PIM-1、PIM-2 和 PIM-3 组成，它们是高度保守的丝氨酸/苏氨酸激酶。这些激酶通过磷酸化调节广泛的底物，并影响关键的细胞过程，如转录、翻译、增殖、凋亡和能量代谢。目前有几种 PIM 抑制剂正在进行临床试验，例如一项用于治疗复发性弥漫性大 B 细胞淋巴瘤的（）的 I 期临床试验已经完成。目前的重点包括 PIM 的结构和生物学特征、正在进行临床试验的小分子抑制剂的研究进展，以及对该领域持续挑战的评估分析。此外，近年来还探索了针对 PIM 的小分子抑制剂的设计和发现，特别关注药物化学，旨在为 PIM 抑制剂的未来发展提供有价值的见解。
