Natural Products Informatics Research Center, Korea Institute of Science and Technology (KIST), Gangneung Institute of Natural Products, (25451) 679, Saimdang-ro, Gangneung-si, Gangwon-do, Republic of Korea.
Natural Products Informatics Research Center, Korea Institute of Science and Technology (KIST), Gangneung Institute of Natural Products, (25451) 679, Saimdang-ro, Gangneung-si, Gangwon-do, Republic of Korea.
Int J Biol Macromol. 2020 Oct 15;161:1086-1098. doi: 10.1016/j.ijbiomac.2020.06.115. Epub 2020 Jun 16.
Hsp90 chaperone is an encouraging target for the development of novel anticancer agents. The failure of Hsp90 inhibitors to get regulatory approval for the treatment of cancer is hindered due to toxicity, cost involved in their development and formulation issues. The inhibitors against this chaperone are also being evaluated in pre-clinical models for the treatment of diseases other than cancer (Alzheimer, malaria, AIDS, etc.). Recently, Hsp90 inhibitors have shown promising senolytic effect that is helpful in increasing the health and life span of mice. The senolytic property of Hsp90 inhibitors will make them less toxic for use in humans. The review focuses on Hsp90 inhibitors discovered till date as senolytic agents along with their future prospects. Further, the various models used for the evaluation of senolytic effect are also discussed.
Hsp90 伴侣蛋白是开发新型抗癌药物的一个有希望的靶点。由于毒性、开发和制剂成本问题，Hsp90 抑制剂未能获得监管部门批准用于癌症治疗。针对这种伴侣蛋白的抑制剂也正在临床前模型中评估用于治疗癌症以外的疾病（阿尔茨海默病、疟疾、艾滋病等）。最近，Hsp90 抑制剂已显示出有希望的衰老细胞选择性杀伤作用，有助于提高小鼠的健康和寿命。Hsp90 抑制剂的衰老细胞选择性杀伤作用将降低其对人类使用的毒性。本综述重点介绍了迄今为止发现的作为衰老细胞选择性杀伤剂的 Hsp90 抑制剂及其未来前景。此外，还讨论了用于评估衰老细胞选择性杀伤作用的各种模型。
