Lin-Lin Zhou, Tao Zhang, Yun Xue, Chuan Yue, Yihui Pan, Pengyu Wang, Teng Yang, Meixia Li, Hu Zhou, Kan Ding, Jianhua Gan, Hongbin Ji, Cai-Guang Yang
Chemo-activation of mitochondrial ClpP exhibits promising anticancer properties. However, we are currently unaware of any studies using selective and potent ClpP activators in lung squamous cell carcinoma. In this work, we report on such an activator, ZK53, which exhibits therapeutic effects on lung squamous cell carcinoma in vivo. The crystal structure of ZK53/ClpP complex reveals a π-π stacking effect that is essential for ligand binding selectively to the mitochondrial ClpP. ZK53 features on a simple scaffold, which is distinct from the activators with rigid scaffolds, such as acyldepsipeptides and imipridones...
November 3, 2023: Nature Communications