Dehydrocurvularin is a potent antineoplastic agent irreversibly blocking ATP-citrate lyase: evidence from chemoproteomics

• Published in: Chemical communications (Cambridge, England) Vol. 55; no. 29; pp. 4194 - 4197
• Main Authors: Deng, Zhangshuang, Wong, Nai-Kei, Guo, Zhiyong, Zou, Kun, Xiao, Youli, Zhou, Yiqing
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 04.04.2019
• Subjects: antineoplastic agents; Antineoplastic Agents - pharmacology; ATP Citrate (pro-S)-Lyase - antagonists & inhibitors; ATP Citrate (pro-S)-Lyase - metabolism; ATP citrate synthase; Cell Proliferation - drug effects; chemical reactions; dehydrocurvularin; Enzyme Inhibitors - pharmacology; HeLa Cells; Humans; mechanism of action; Proteomics; Zearalenone - analogs & derivatives; Zearalenone - pharmacology

Natural-product macrolide 10,11-dehydrocurvularin ( DCV ) was revealed to be a potent irreversible inhibitor of ATP-citrate lyase (ACLY) via classical chemoproteomic profiling, which mechanistically illuminates the anti-cancer mode of action of DCV and its analogues. Dehydrocurvularin irreversibly i...