Liao Senyi, Wu Guang, Xie Zhizhong, Lei Xiaoyong, Yang Xiaoyan, Huang Sheng, Deng Xiangping, Wang Zhe, Tang Guotao
Institute of Pharmacy and Pharmacology, Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China.
The Second Affiliated Hospital, Department of Pharmacy, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
Eur J Med Chem. 2024 Mar 5;267:116170. doi: 10.1016/j.ejmech.2024.116170. Epub 2024 Feb 1.
As an important characteristic of tumor, acidic tumor microenvironment (TME) is closely related to immune escape, invasion, migration and drug resistance of tumor. The acidity of the TME mainly comes from the acidic products produced by the high level of tumor metabolism, such as lactic acid and carbon dioxide. pH regulators such as monocarboxylate transporters (MCTs), carbonic anhydrase IX (CA IX), and Na/H exchange 1 (NHE1) expel protons directly or indirectly from the tumor to maintain the pH balance of tumor cells and create an acidic TME. We review the functions of several pH regulators involved in the construction of acidic TME, the structure and structure-activity relationship of pH regulator inhibitors, and provide strategies for the development of small-molecule antitumor inhibitors based on these targets.
作为肿瘤的一个重要特征，酸性肿瘤微环境（TME）与肿瘤的免疫逃逸、侵袭、迁移和耐药性密切相关。TME的酸性主要来自肿瘤高代谢产生的酸性产物，如乳酸和二氧化碳。单羧酸转运体（MCTs）、碳酸酐酶IX（CA IX）和钠/氢交换体1（NHE1）等pH调节剂直接或间接将质子排出肿瘤，以维持肿瘤细胞的pH平衡并营造酸性TME。我们综述了几种参与构建酸性TME的pH调节剂的功能、pH调节剂抑制剂的结构及构效关系，并基于这些靶点提供了小分子抗肿瘤抑制剂的开发策略。
