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Beyond the BET Family: Targeting CBP/p300 with 4‐Acyl Pyrroles
Author(s) -
Hügle Martin,
Lucas Xavier,
Ostrovskyi Dmytro,
Regenass Pierre,
Gerhardt Stefan,
Einsle Oliver,
Hau Mirjam,
Jung Manfred,
Breit Bernhard,
Günther Stefan,
Wohlwend Daniel
Publication year - 2017
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201705516
Subject(s) - bromodomain , bet inhibitor , cancer research , breast cancer , cancer , chemistry , cancer cell , computational biology , acetylation , biology , biochemistry , genetics , gene
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.