Antagonist of EP300, CREBBP
Protein target names: EP300, CREBBP
Mechanism of action: Antagonist
In Vitro Validations
DOI Reference: 10.1016/j.chembiol.2015.10.013
In Cell Validations
In Vivo Data
No in Vivo Validations
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SERP ratings and comments
The biochemical, cellular and ITC data reported in the reference (Chem Biol 2015, 22, 1588-1596) support the use of PF-CBP1 as a selective probe for the interrogation of the function of CBP bromodomain in cells. In a slightly later publication (10.1021/acs.jmedchem.6b01022), however, the selectivity versus BRD4 using a different biochemical assay format is reported as being in the 10-fold range rather than 100-fold.
(last updated: 28 Mar 2017 )
I believe this is the best CRBP probe available, but it is far from ideal. It is only weakly potent. Ideally it would be <100 nM but it is only active in cells at or above 1 uM. The margin to BRD4 potency (18 uM) is ~100-fold based on FP but is worse in the Bromoscan panel, so care must be taken not to use it at a concentration that causes BRD4 inhibition. Given that BRD4 inhibitors show a drop off in potency of ~10-fold in cells, I would suggest at concentration of 1-10 uM so this compound will not inhibit BRD4. The compound is also potent against EP300 due to close homology with CRBP and other BRDs are inhibited with <100-fold selectivity.
(last updated: 6 Apr 2017 )
PF-CBP1 mildly downregulated expression of key inflammatory genes (e.g., IL6, IL1B, IFNB, TNF) in J774, a murine macrophage cell line, at concentrations typically >/=1 uM and did not show cytotoxicity. Additionally, the compound downregulated RGS4 (a CBP-downstream target gene linked to Parkinson’s disease) in neurons. No in vivo model organism data is available as of yet.
(last updated: 26 Jul 2017 )