338755-15-0Relevant academic research and scientific papers
Structure-based design, synthesis and biological evaluation of a novel series of isoquinolone and pyrazolo[4,3-c]pyridine inhibitors of fascin 1 as potential anti-metastatic agents
Francis, Stuart,Croft, Daniel,Schüttelkopf, Alexander W.,Parry, Charles,Pugliese, Angelo,Cameron, Ken,Claydon, Sophie,Drysdale, Martin,Gardner, Claire,Gohlke, Andrea,Goodwin, Gillian,Gray, Christopher H.,Konczal, Jennifer,McDonald, Laura,Mezna, Mokdad,Pannifer, Andrew,Paul, Nikki R.,Machesky, Laura,McKinnon, Heather,Bower, Justin
supporting information, p. 1023 - 1029 (2019/02/19)
Fascin is an actin binding and bundling protein that is not expressed in normal epithelial tissues but overexpressed in a variety of invasive epithelial tumors. It has a critical role in cancer cell metastasis by promoting cell migration and invasion. Here we report the crystal structures of fascin in complex with a series of novel and potent inhibitors. Structure-based elaboration of these compounds enabled the development of a series with nanomolar affinities for fascin, good physicochemical properties and the ability to inhibit fascin-mediated bundling of filamentous actin. These compounds provide promising starting points for fascin-targeted anti-metastatic therapies.
