Beyond the BET Family: Targeting CBP/p300 with 4‐Acyl Pyrroles. Issue 41 (7th September 2017)

• Record Type: Journal Article
• Authors: Hügle, Martin; Lucas, Xavier; Ostrovskyi, Dmytro; Regenass, Pierre; Gerhardt, Stefan; Einsle, Oliver; Hau, Mirjam; Jung, Manfred; Breit, Bernhard; Günther, Stefan; Wohlwend, Daniel
• Is Part Of: Angewandte Chemie international edition. Volume 56:Issue 41(2017)
• Page Start: 12476
• Page End: 12480
• Publication Date: 2017-09-07
• Subjects: 4-acyl pyrroles -- bromodomains -- CBP -- drug discovery -- p300; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201705516
• Languages: English
• ISSNs: 1433-7851

Abstract

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. Abstract : You better you BET : XDM‐CBP is a highly potent and selective inhibitor for the bromodomains (BRDs) of CBP and p300 derived from a pan‐selective BET (bromodomain and extra‐terminal domain) 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.