Peer-Reviewed Publication
J Med Chem2026August 18, 2026Journal Article
Discovery of Monoterpenoid Indole Alkaloids Targeting CCN1 to Suppress Autophagy for the Treatment of Hypoxic Kidney Injury.
Xue Qiao1,2,3, Shun-Qing Chen1,4, Ariel M Sarotti5, Jixian Zhang6, Yu-Ting Zhong1,4, Wei-Chen Chen1,4, Xiaofen Wang4, Wumei Wang7, Jianying Huang4, Xiao-Yan Wu1, Hui-Ming Wang1, Shugeng Cao8, Zhengqiu Li6, Qihao Wu9, Yuling Xiao2,3, Xuechuan Hong10,7, You-Sheng Cai1,4
1Department of Nephrology, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan430071, China.
2State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai201203, China.
3Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai264117, China.
4Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (MOE), Clinical Trial Center, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan430071, China.
5Facultad de Ciencias Bioquimicas y Farmaceuticas, Instituto de Quimica Rosario (CONICET), Universidad Nacional de Rosario, Rosario2000, Argentina.
6State Key Laboratory of Bioactive Molecules and Druggability Assessment, International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development (MOE), and School of Pharmacy, Jinan University, Guangzhou510632, China.
7Key Laboratory of Biodiversity and Environment on the Qinghai-Tibetan Plateau, Ministry of Education, School of Ecology and Environment, Tibet University, Lhasa850000, China.
8Department of Pharmaceutical Sciences, Daniel K. Inouye College of Pharmacy, University of Hawai'i at Hilo, Hilo, Hawaii96720, United States.
9Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania15261, United States.
10School of Pharmaceutical Sciences, Key Laboratory of Smart Drug Delivery, Ministry of Education, National Key Laboratory of Advanced Drug Formulations for Overcoming Delivery Barriers, Fudan University, Shanghai201203, China.
Abstract
Hypoxic kidney injury remains difficult to treat due to the lack of therapies that effectively prevent podocyte injury and disease progression. Bioassay-guided investigation of Tabernaemontana pandacaqui yielded ten monoterpenoid indole alkaloids (MIAs), including eight new compounds with five unprecedented carbon skeletons. Notably, compound 6 is the first MIA monomer with a 6/5/6/5/6 pentacyclic…
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