Natural Product Micheliolide (MCL) Irreversibly Activates Pyruvate Kinase M2 and Suppresses Leukemia

• Published in: Journal of medicinal chemistry Vol. 61; no. 9; pp. 4155 - 4164
• Main Authors: Li, Jing, Li, Shanshan, Guo, Jianshuang, Li, Qiuying, Long, Jing, Ma, Cheng, Ding, Yahui, Yan, Chunli, Li, Liangwei, Wu, Zhigang, Zhu, He, Li, Keqin Kathy, Wen, Liuqing, Zhang, Quan, Xue, Qingqing, Zhao, Caili, Liu, Ning, Ivanov, Ivaylo, Luo, Ming, Xi, Rimo, Long, Haibo, Wang, Peng George, Chen, Yue
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 10.05.2018; American Chemical Society (ACS)
• Subjects: 60 APPLIED LIFE SCIENCES; Acetylation - drug effects; Active Transport, Cell Nucleus - drug effects; Amino Acid Sequence; Animals; Antineoplastic Agents - pharmacology; Carcinogenesis - drug effects; Carrier Proteins - chemistry; Carrier Proteins - metabolism; Cell Line, Tumor; Cell Nucleus - drug effects; Cell Nucleus - metabolism; Enzyme Activation - drug effects; Gene Expression Regulation, Neoplastic - drug effects; Humans; Leukemia - pathology; Membrane Proteins - chemistry; Membrane Proteins - metabolism; Pharmacology & Pharmacy; Phosphorylation - drug effects; Protein Domains; Protein Multimerization; Protein Structure, Quaternary; Sesquiterpenes, Guaiane - pharmacology; Substrate Specificity; Thyroid Hormone-Binding Proteins; Thyroid Hormones - chemistry; Thyroid Hormones - metabolism; Xenograft Model Antitumor Assays; Zebrafish

Metabolic reprogramming of cancer cells is essential for tumorigenesis in which pyruvate kinase M2 (PKM2), the low activity isoform of pyruvate kinase, plays a critical role. Herein, we describe the identification of a nature-product-derived micheliolide (MCL) that selectively activates PKM2 through...