Design and Synthesis of Senescence-Targeted Prodrugs with Senomorphic and Senolytic Properties To Mitigate Chemotherapy-Induced Kidney Injury.

Lele Ding, Xi Wang, Qian Liu, Yuxuan Zhang, Xinyu Wu, Biying Xiao, Dan Liu, Lu Chen, Hairong Zeng, Bei Zhao, Changsheng Dong, Lihui Li, Guangbo Ge, Lijun Jia, Shuaishuai Ni

Cancer Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.Cancer Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China. · pubmed

Paper

Abstract

Senotherapeutic agents hold great potential for mitigating chemotherapy-induced kidney injury. However, the heterogeneity of cellular senescence complicates their application, as early stage senescent cells (SnCs) play beneficial roles in kidney damage repair. Senotherapeutics are broadly categorized into two classes: senolytics, which selectively eliminate SnCs, and senomorphics, which suppress the senescence-associated secretory phenotype (SASP) without killing them. Herein, we repurposed an antioxidant agent, bardoxolone methyl (CDDOMe), as a novel senomorphic agent to mitigate the chemotherapy-induced kidney injury and subsequently modified it into a series of senescence-associated β-galactosidase (SA-β-gal) activated prodrugs. The optimal prodrug,

The following analysis is generated by AI and may contain errors. It is separate from the authors’ abstract and is not peer review.

Research summary

The paper claims to develop senescence-targeted prodrugs that mitigate chemotherapy-induced kidney injury by utilizing senomorphic and senolytic properties. This research is relevant as it addresses cellular senescence, a key factor in aging and age-related diseases, and explores therapeutic strategies that could potentially improve healthspan by targeting the underlying mechanisms of senescence.

Author of this paper? Send a correction.