title: In silico identification of natural product inhibitors of JAK2.
abstract: Emodic acid (1) and 6-chloroemodic acid (2) have been identified from a natural product database as useful scaffolds for the future development of novel JAK2 inhibitors using structure-based high-throughput virtual screening. Low-energy binding conformations of 1 and 2 in the JAK2 PTK domain were generated by virtual ligand docking and were found to overlap considerably with the binding pose of CMP6, a known JAK2 inhibitor. Compounds 1 and 2 displayed low micromolar efficacies against JAK2 enzyme activity and JAK2 autophosphorylation in human erythroleukemia cells, and inhibited STAT3 DNA-binding activity in a human hepatocarcinoma cell line.
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
authors.forename: Hai-Jing
authors.initials: HJ
authors.lastname: Zhong
authors.affiliation: Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
authors.forename: I Lam
authors.initials: IL
authors.lastname: Tam
authors.affiliation: Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China.
authors.forename: Daniel Shiu-Hin
authors.initials: DS
authors.lastname: Chan
authors.affiliation: Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China. Electronic address: edmondma@hkbu.edu.hk.
authors.forename: Dik-Lung
authors.initials: DL
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China. Electronic address: duncanleung@umac.mo.
authors.forename: Chung-Hang
authors.initials: CH
authors.lastname: Leung
mesh_terms: D001665:Binding Sites; D045744:Cell Line, Tumor; D003198:Computer Simulation; D062126:Databases, Chemical; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000737:chemistry*; D017434:Protein Structure, Tertiary
chemical_list: D047428:Protein Kinase Inhibitors; D053614:Janus Kinase 2
keywords: 6-Chloroemodic acid; Emodic acid; JAK2; Natural product; Virtual screening