National Center for
3ODK: Discovery Of Cell-Active Phenyl-Imidazole Pin1 Inhibitors By Structure-Guided Fragment Evolution
Bioorg. Med. Chem. Lett. (2010) 20 p.6483-6488
Pin1 is an emerging oncology target strongly implicated in Ras and ErbB2-mediated tumourigenesis. Pin1 isomerizes bonds linking phospho-serine/threonine moieties to proline enabling it to play a key role in proline-directed kinase signalling. Here we report a novel series of Pin1 inhibitors based on a phenyl imidazole acid core that contains sub-muM inhibitors. Compounds have been identified that block prostate cancer cell growth under conditions where Pin1 is essential.