کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1371590 | 981849 | 2010 | 6 صفحه PDF | دانلود رایگان |
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-μM inhibitors. Compounds have been identified that block prostate cancer cell growth under conditions where Pin1 is essential.
Structure-guided techniques were used to evolve a 5-pyridinyl pyrazole-3-carboxylate fragment into a series of 5-aryl-carbamoyl-3-phenyl-imidazole-4-carboxylates, examples of which inhibited the Pin1 PPIase with sub-μM IC50 and blocked proliferation of prostate cancer cells.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 20, Issue 22, 15 November 2010, Pages 6483–6488