Fu Ying, Saxu Rengui, Ahmad Ridwan Kadir, Zhao Cai, Kong Xiangshun, Rong Yao, Zheng Weida, Yu Peng, Teng Yuou
China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Bioengineering, Tianjin University of Science and Technology Tianjin 300457 China
Medical College, Yanbian University No.977 Gongyuan Road Yanji City Jilin Province 133002 P. R. China.
RSC Adv. 2022 Aug 8;12(34):21821-21826. doi: 10.1039/d2ra01882a. eCollection 2022 Aug 4.
Axitinib is a potent vascular endothelial growth factor receptor (VEGFR) inhibitor, which has a strong inhibitory effect on the three isoforms of VEGFR 1-3. Having strong therapeutic efficacy, its broad use is limited by its side effects such as hypertension, proteinuria, cardiovascular damage, and liver and kidney dysfunction. Selenium compounds are broadly reported to have a good protective effect on cardiovascular disease, inflammation, infection, and immune function. In this study, a selenium substitute of axitinib was synthesized, and its anti-renal cell carcinoma activity and side effects were investigated. The results of the study indicated that Se-axitinib had potent antitumor activity on renal cell carcinoma (RCC), alleviated vascular hyperpermeability, and also alleviated axitinib-related side effects including hypertension, liver dysfunction and kidney dysfunction significantly. Therefore, we suggest that Se-axitinib could be a solution to the severe side effects of VEGFR inhibitors and provide evidence to improve the outcome of RCC treatment.
阿昔替尼是一种有效的血管内皮生长因子受体（VEGFR）抑制剂，对VEGFR 1-3的三种异构体具有强大的抑制作用。尽管其具有强大的治疗效果，但其广泛应用受到诸如高血压、蛋白尿、心血管损伤以及肝肾功能障碍等副作用的限制。大量报道表明，硒化合物对心血管疾病、炎症、感染及免疫功能具有良好的保护作用。在本研究中，合成了阿昔替尼的一种硒替代物，并对其抗肾细胞癌活性及副作用进行了研究。研究结果表明，硒代阿昔替尼对肾细胞癌（RCC）具有强大的抗肿瘤活性，可减轻血管通透性过高，还能显著减轻包括高血压、肝功能障碍和肾功能障碍在内的与阿昔替尼相关的副作用。因此，我们认为硒代阿昔替尼可能是解决VEGFR抑制剂严重副作用的一种方法，并为改善RCC治疗结果提供了证据。
