Liu Zhenyang, Gao Hongwei, Zhao Ziyu, Huang Mengrui, Wang Shengnan, Zhan Jiuyu
School of Life Science, Ludong University, Yantai, Shandong 264025, China.
School of Life Science, Ludong University, Yantai, Shandong 264025, China.
Biomed Pharmacother. 2023 Jan;157:113990. doi: 10.1016/j.biopha.2022.113990. Epub 2022 Nov 29.
Protein tyrosine phosphatase 1B (PTP1B) is a crucial therapeutic target for multiple human diseases comprising type 2 diabetes (T2DM) and obesity because it is a seminal part of a negative regulator in both insulin and leptin signaling pathways. PTP1B inhibitors increase insulin receptor sensitivity and have the ability to cure insulin resistance-related diseases. However, the few PTP1B inhibitors that entered the clinic (Ertiprotafib, ISIS-113715, Trodusquemine, and JTT-551) were discontinued due to side effects or low selectivity. Molecules with broad chemical diversity extracted from natural products have been reported to be potent PTP1B inhibitors with few side effects. This article summarizes the recent PTP1B inhibitors extracted from natural products, clarifying the current research progress, and providing new options for designing new and effective PTP1B inhibitors.
蛋白酪氨酸磷酸酶1B(PTP1B)是包括2型糖尿病(T2DM)和肥胖症在内的多种人类疾病的关键治疗靶点,因为它是胰岛素和瘦素信号通路中负调节因子的重要组成部分。PTP1B抑制剂可提高胰岛素受体敏感性,并能够治愈与胰岛素抵抗相关的疾病。然而,少数进入临床试验的PTP1B抑制剂(依替泊他芬、ISIS-113715、曲度司他和JTT-551)因副作用或低选择性而被停用。据报道,从天然产物中提取的具有广泛化学多样性的分子是有效的PTP1B抑制剂,且副作用较少。本文总结了最近从天然产物中提取的PTP1B抑制剂,阐明了当前的研究进展,并为设计新型有效的PTP1B抑制剂提供了新的选择。