Literature DB >> 26321360

N-Hydroxyimides and hydroxypyrimidinones as inhibitors of the DNA repair complex ERCC1-XPF.

Timothy M Chapman1, Claire Wallace1, Kevin J Gillen1, Preeti Bakrania1, Puneet Khurana1, Peter J Coombs1, Simon Fox1, Emilie A Bureau1, Janet Brownlees1, David W Melton2, Barbara Saxty1.   

Abstract

A high throughput screen allowed the identification of N-hydroxyimide inhibitors of ERCC1-XPF endonuclease activity with micromolar potency, but they showed undesirable selectivity profiles against FEN-1. A scaffold hop to a hydroxypyrimidinone template gave compounds with similar potency but allowed selectivity to be switched in favour of ERCC1-XPF over FEN-1. Further exploration of the structure-activity relationships around this chemotype gave sub-micromolar inhibitors with >10-fold selectivity for ERCC1-XPF over FEN-1.
Copyright © 2015 Elsevier Ltd. All rights reserved.

Entities:  

Keywords:  DNA repair; ERCC1–XPF; Hydroxypyrimidinone; N-Hydroxyimide

Mesh：

Substances：

Year:  2015        PMID： 26321360     DOI： 10.1016/j.bmcl.2015.08.024

Source DB:  PubMed          Journal:  Bioorg Med Chem Lett        ISSN： 0960-894X            Impact factor:   2.823


  9 in total

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9.  Computational Characterization of Small Molecules Binding to the Human XPF Active Site and Virtual Screening to Identify Potential New DNA Repair Inhibitors Targeting the ERCC1-XPF Endonuclease.

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  9 in total

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