Beyond the BET Family: Targeting CBP/p300 with 4-Acyl Pyrroles
Hügle M, Lucas X, Ostrovskyi D, Regenass P, Gerhardt S, Einsle O, Hau M, Jung M, Breit B, Günther S, Wohlwend D
Angew Chem Int Ed Engl. online article
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 CBPare less studied. XDMCBP 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 crystalstructure 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.
