Discovery of wrightiadione as a novel template for the TrkA kinase inhibitors. Issue 22 (15th November 2015)

• Record Type: Journal Article
• Authors: Jeong, Yujeong; Lim, Sang Min; Hong, Sungwoo
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 25:Issue 22(2015)
• Page Start: 5186
• Page End: 5189
• Publication Date: 2015-11-15
• Subjects: Kinase -- Trk inhibitor -- Wrightiadione -- Modeling -- Anticancer; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2015.09.070
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: 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 compound2h with biochemical potency at the single-digit micromolar level.