title: Discovery of wrightiadione as a novel template for the TrkA kinase inhibitors.
abstract: Enzymatic kinase assays and docking simulation studies have shown that the natural product wrightiadione displays inhibitory activity toward TrkA and PLK3. In this study, the template of wrightiadione served as a starting point for Trk inhibitor development campaigns. Molecular simulation provided structural insights for the design of derivatives that were efficiently generated by our recently developed 3-step tandem synthetic approach, resulting in the discovery of compound 2h with biochemical potency at the single-digit micromolar level.
authors.affiliation: Center for Catalytic Hydrocarbon Functionalization, Institute for Basic Science (IBS), Daejeon 305-701, Republic of Korea; Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Republic of Korea.
authors.forename: Yujeong
authors.initials: Y
authors.lastname: Jeong
authors.affiliation: Center for Catalytic Hydrocarbon Functionalization, Institute for Basic Science (IBS), Daejeon 305-701, Republic of Korea.
authors.forename: Sang Min
authors.initials: SM
authors.lastname: Lim
authors.affiliation: Center for Catalytic Hydrocarbon Functionalization, Institute for Basic Science (IBS), Daejeon 305-701, Republic of Korea; Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Republic of Korea. Electronic address: hongorg@kaist.ac.kr.
authors.forename: Sungwoo
authors.initials: S
authors.lastname: Hong
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry*; D006801:Humans; D007192:Indenes / Q000737:chemistry*; D007529:Isoflavones / Q000737:chemistry*; D062105:Molecular Docking Simulation; D047428:Protein Kinase Inhibitors / Q000737:chemistry*; D011804:Quinolines / Q000737:chemistry*; D020917:Receptor, trkA / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: C000609111:8-methoxy-5-methyl-5H-indeno(2,1-b(quinoline-6,11-dione; D000972:Antineoplastic Agents, Phytogenic; D007192:Indenes; D007529:Isoflavones; D047428:Protein Kinase Inhibitors; D011804:Quinolines; C000602495:wrightiadione; D020917:Receptor, trkA
keywords: Anticancer; Kinase; Modeling; Trk inhibitor; Wrightiadione