Jason D Katz, Andrew Haidle, Kaleen K Childers, Anna A Zabierek, James P Jewell, Yongquan Hou, Michael D Altman, Alexander Szewczak, Dapeng Chen, Andreas Harsch, Mansuo Hayashi, Lee Warren, Michael Hutton, Hugh Nuthall, Hua-Poo Su, Sanjeev Munshi, Matt G Stanton, Ian W Davies, Ben Munoz, Alan Northrup
The initial structure activity relationships around an isoindoline uHTS hit will be described. Information gleaned from ligand co-crystal structures allowed for rapid refinements in both MARK potency and kinase selectivity. These efforts allowed for the identification of a compound with properties suitable for use as an in vitro tool compound for validation studies on MARK as a viable target for Alzheimer's disease.
October 22, 2016: Bioorganic & Medicinal Chemistry Letters