State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
Key Laboratory of Drug Targeting and Drug Delivery System of Ministry of Education, West China School of Pharmacy, Sichuan University, Sichuan 610041, China.
Bioorg Med Chem Lett. 2019 Sep 15;29(18):2595-2603. doi: 10.1016/j.bmcl.2019.08.001. Epub 2019 Aug 2.
Inhibitors of the Hippo signaling pathway have been demonstrated to have a potential clinical application in cases such as tissue repair and organ regeneration. However, there is a lack of potent Hippo pathway inhibitors at present. Herein we report the discovery of a series of 1,8-disubstituted-[1,2,3]triazolo[4,5-c]quinoline derivatives as a new class of Hippo pathway inhibitors by utilizing a cell line-based screening model (A549-CTGF). Structure-activity relationship (SAR) of these compounds was also discussed. The most potent compound in the A549-CTGF cell assay, 11g, was then evaluated by real-time PCR and immunofluorescence assays. Overall, this study provides a starting point for later drug discovery targeting the Hippo signaling pathway.
Hippo 信号通路抑制剂在组织修复和器官再生等方面具有潜在的临床应用价值。然而，目前缺乏有效的 Hippo 通路抑制剂。本研究利用基于细胞系的筛选模型（A549-CTGF），发现了一系列 1,8-取代-[1,2,3]三唑并[4,5-c]喹啉衍生物，作为 Hippo 通路抑制剂的一个新类别。还讨论了这些化合物的构效关系（SAR）。在 A549-CTGF 细胞测定中，最有效的化合物 11g 随后通过实时 PCR 和免疫荧光测定进行了评估。总的来说，这项研究为以后针对 Hippo 信号通路的药物发现提供了一个起点。
