Structure-based design of novel human Pin1 inhibitors (I)

…, T VanArsdale, I Popoff, J Piraino, S Margosiak…

Index: Guo, Chuangxing; Hou, Xinjun; Dong, Liming; Dagostino, Eleanor; Greasley, Samantha; Ferre, RoseAnn; Marakovits, Joseph; Johnson, M. Catherine; Matthews, David; Mroczkowski, Barbara; Parge, Hans; VanArsdale, Todd; Popoff, Ian; Piraino, Joseph; Margosiak, Stephen; Thomson, James; Los, Gerrit; Murray, Brion W. Bioorganic and Medicinal Chemistry Letters, 2009 , vol. 19, # 19 p. 5613 - 5616

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Citation Number: 50

Abstract

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 ...

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