Structure-based identification of inhibitory fragments targeting the p300/CBP-associated factor bromodomain

  • The P300/CBP-associated factor plays a central role in retroviral infection and cancer development, and the C-terminal bromodomain provides an opportunity for selective targeting. Here, we report several new classes of acetyl-lysine mimetic ligands ranging from mM to low micromolar affinity that were identified using fragment screening approaches. The binding modes of the most attractive fragments were determined using high resolution crystal structures providing chemical starting points and structural models for the development of potent and selective PCAF inhibitors.

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Author:Apirat ChaikuadORCiD, Steffen Lang, Paul E. BrennanORCiD, Claudia Temperini, Oleg FedorovORCiD, Johan Hollander, Ruta Nachane, Chris Abell, Susanne Müller, Gregg Siegal, Stefan KnappORCiD
Pubmed Id:
Parent Title (English):Journal of medicinal chemistry
Publisher:American Chemical Society
Place of publication:Washington, DC
Document Type:Article
Date of Publication (online):2016/11/09
Date of first Publication:2016/01/05
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2016/11/09
Page Number:6
First Page:1648
Last Page:1653
This is an open access article published under a Creative Commons Attribution (CC-BY) License, which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Institutes:Biochemie, Chemie und Pharmazie / Biochemie und Chemie
Biowissenschaften / Biowissenschaften
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0