CPI-637

Antagonist of EP300, CREBBP

Structure

Information

Protein target names: EP300 CREBBP

Mechanism of action: Antagonist

In Vitro Validations

Uniprot ID: Q09472
Target Class:
Target SubClass: Bromodomain
Potency: IC 50
Potency Value: 51 nM
Potency Assay: TR-FRET assay
PDB ID for probe-target interaction (3D structure): --
Structure-activity relationship: Yes, see ACS Med Chem Lett paper
Target aliases:
Histone acetyltransferase p300, P300, EP300, EP300 ...

DOI Reference: 10.1021/acsmedchemlett.6b00075

In Cell Validations

In Vivo Data

No in Vivo Validations

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SERP ratings and comments


SERP Ratings

In Cell Rating

Comments:

This is a high quality probe that is appropriate for interrogating CBP/EP300 cell biology in certain circumstances. CPI-637 is structurally differentiated from other CBP/EP300 chemical probes, and thus adds value to the bromodomain chemical probe toolbox. The enantiomer is also reported, which is substantially weaker and may, therefore, be of use as a negative control. I disagree with the comment (Taylor et al, ACS Med Chem Lett 2016) that BRD9 potency is 'acceptable' as this will be context-dependent, depending on how the probe is used. Inhibition of MYC expression by the probe is not a direct measure of CBP/EP300 target engagement. The limited off-target profiling (both within the bromodomain family and beyond) is a weakness of this probe - broader off-target profiling is recommended.

(last updated: 15 May 2017 )

SERP Ratings

In Cell Rating

Comments:

This is a high quality compound originating from a dedicated medicinal chemistry effort to arrive at a molecule with 30/51 nM IC50 against CBP/EP300 in TR-FRET assays that causes cellular phenotypes below 1 uM. Selectivity over the BRD4 BD1 is >700-fold, however the compound also inhibits the bromodomain of BRD9 in biochemical assays at concentrations below 1 uM. A limitation in the characterization of this compound is that in total it has only been profiled against 15 bromodomains and no information is available on off-targets in cellular assays.  

(last updated: 17 Nov 2020 )