I-CBP112 is a ligand of the highly conserved bromodomain of both CBP and p300. In vitro, the probe displays selective binding to CBP/p300 bromodomains with a Kd ~600 nM. Comparatively, the Kd for the bromodomains of BRD4 are ~5 and ~20 micromolar, so some off-target effects may be observed at higher concentrations in cells. Notably, I-CBP112 does not seem to displace CBP/p300 from acetylated chromatin, so cellular effects may be through as-of-yet undetermined mechanisms, perhaps through allosteric modulation (PMID:27332697). No pharmacokinetic data in animals has been published for this probe at this time, so its utility in model organisms remains to determined.
31 Mar 2017 )