| Literature DB >> 28766825 |
Martin Hügle1, Xavier Lucas2, Dmytro Ostrovskyi3, Pierre Regenass3, Stefan Gerhardt1, Oliver Einsle1,4,5, Mirjam Hau6, Manfred Jung6, Bernhard Breit4,3, Stefan Günther6,4, Daniel Wohlwend1.
Abstract
Bromodomain and extra-terminal domain (BET) inhibitors are widely used both as chemical tools to study the biological role of their targets in living organisms and as candidates for drug development against several cancer variants and human disorders. However, non-BET bromodomains such as those in p300 and CBP are less studied. XDM-CBP is a highly potent and selective inhibitor for the bromodomains of CBP and p300 derived from a pan-selective BET BRD-binding fragment. Along with X-ray crystal-structure analysis and thermodynamic profiling, XDM-CBP was used in screenings of several cancer cell lines in vitro to study its inhibitory potential on cancer cell proliferation. XDM-CBP is demonstrated to be a potent and selective CBP/p300 inhibitor that acts on specific cancer cell lines, in particular malignant melanoma, breast cancer, and leukemia.Entities:
Keywords: 4-acyl pyrroles; CBP; bromodomains; drug discovery; p300
Year: 2017 PMID： 28766825 DOI： 10.1002/anie.201705516
Source DB: PubMed Journal: Angew Chem Int Ed Engl ISSN： 1433-7851 Impact factor: 15.336