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ID: ALA1156037

Journal: Bioorg Med Chem Lett

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

Authors: Guo C, Hou X, Dong L, Dagostino E, Greasley S, Ferre R, Marakovits J, Johnson MC, Matthews D, Mroczkowski B, Parge H, Vanarsdale T, Popoff I, Piraino J, Margosiak S, Thomson J, Los G, Murray BW.

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 chemistry approaches, resulting in a more attractive lead series.

CiteXplore: 19729306

DOI: 10.1016/j.bmcl.2009.08.034