title: Virtual screening and optimization of Type II inhibitors of JAK2 from a natural product library.
abstract: Amentoflavone has been identified as a JAK2 inhibitor by structure-based virtual screening of a natural product library. In silico optimization using the DOLPHIN model yielded analogues with enhanced potency against JAK2 activity and HCV activity in cellulo. Molecular modeling and kinetic experiments suggested that the analogues may function as Type II inhibitors of JAK2.
authors.affiliation: Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China. edmondma@hkbu.edu.hk.
authors.forename: Dik-Lung
authors.initials: DL
authors.lastname: Ma
authors.forename: Daniel Shiu-Hin
authors.initials: DS
authors.lastname: Chan
authors.forename: Guo
authors.initials: G
authors.lastname: Wei
authors.forename: Hai-Jing
authors.initials: HJ
authors.lastname: Zhong
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.forename: Lai To
authors.initials: LT
authors.lastname: Leung
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Gullen
authors.forename: Pauline
authors.initials: P
authors.lastname: Chiu
authors.forename: Yung-Chi
authors.initials: YC
authors.lastname: Cheng
authors.forename: Chung-Hang
authors.initials: CH
authors.lastname: Leung
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D016174:Hepacivirus / Q000187:drug effects; D006801:Humans; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007700:Kinetics; D008958:Models, Molecular; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000998:Antiviral Agents; D001688:Biological Products; D047428:Protein Kinase Inhibitors; D054852:Small Molecule Libraries; C507924:JAK2 protein, human; D053614:Janus Kinase 2