School of Pharmacy, Jinan University; Guangzhou City Key Laboratory of Precision Chemical Drug Development; International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development, Ministry of Education (MOE) of People's Republic of China, 601 Huangpu Avenue West, Guangzhou, 510632, China.
Chem Commun (Camb). 2019 Jan 31;55(11):1596-1599. doi: 10.1039/c8cc08753a.
Pancreatic cancer has been defined as one of the most complex and challenging cancers to treat, but very few valid therapeutic targets have been identified to date. To address this issue, a 61-compound library was readily created by Ugi reaction followed by phenotypic screening, leading to the discovery of two most potent inhibitors, P21 and P26, which significantly impair BxPC-3 pancreatic cancer cell survival. A series of interacting protein hits, such as GSTO1, FAM213A, RAB6A/6B/39A and USMG5, were subsequently identified by quantitative chemoproteomics studies. The main cellular target, GSTO1, was further validated as a novel pancreatic cancer therapeutic target.
胰腺癌被定义为最难治疗的癌症之一，但迄今为止仅发现了极少数有效的治疗靶点。为了解决这个问题，我们通过 Ugi 反应快速构建了一个 61 种化合物库，然后进行表型筛选，发现了两种最有效的抑制剂 P21 和 P26，它们显著抑制 BxPC-3 胰腺癌细胞的存活。通过定量化学蛋白质组学研究，随后鉴定出一系列相互作用的蛋白靶点，如 GSTO1、FAM213A、RAB6A/6B/39A 和 USMG5。主要的细胞靶标 GSTO1 进一步被验证为一种新的胰腺癌治疗靶点。
