کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1371857 | 981857 | 2009 | 4 صفحه PDF | دانلود رایگان |
Pin1 is a member of the cis–trans peptidyl-prolyl isomerase family with potential anti-cancer therapeutic value. Here we report structure-based de novo design and optimization of novel Pin1 inhibitors. Without a viable lead from internal screenings, we designed a series of novel Pin1 inhibitors by interrogating and exploring a protein crystal structure of Pin1. The ligand efficiency of the initial concept molecule was optimized with integrated SBDD and parallel chemistry approaches, resulting in a more attractive lead series.
A series of novel non-peptide small molecular PIN1 inhibitors was discovered utilizing SBDD and combinatorial approach. The simplified pharmacophore opens the door for other drug-like Pin-1 inhibitor design.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 19, Issue 19, 1 October 2009, Pages 5613–5616