PF-CBP1

Reagent Authentication Certificate:

Chemical Probes Portal PF-CBP1.pdf

Protein target name:

CREBBP, EP300

Mechanism of action:

Antagonist

Recommended Concentration for use in cells:

100 nM - 1 uM

Probe Availability

MedChem Express (2070014-93-4)

Tocris (PF CBP1)

Cayman (PF-CBP1)

Probe Information

Target and Probe Information

Target Details

Target class:

Epigenetics

Subclass:

Bromodomain

HUGO ID:

HGNC:2348 HGNC:3373

Entrez gene ID:

1387 2033

UNIPROT ID:

Q09472 Q92793

Target alias:

CREB binding protein, CBP, KAT3A, RSTS, RSTS1, E1A binding protein p300, KAT3B, RSTS2, p300

Probe Details

Chemical Probes Portal ID:

CPP1291

PubChem CID:

119081417

SMILES string:

CCCOC1=CC=C(C=C1)CCC2=NC3=C(N2CCN4CCOCC4)C=CC(=C3)C5=C(ON=C5C)C

InChi Key:

CGWBJJZOKGZCSJ-UHFFFAOYSA-N

Control compound:

ISOX-INACT (isolipophilic inactive isomer)

Orthogonal probe:

SGC-CBP30I-CBP112GNE-049

Physico-chemical properties

Potential reactivities:

None

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

190 nM

Potency assay:

Isothermal titration calorimetry

Structure-activity relationship:

Yes; further details will be described in due course

Off target activity

Potency (off target):

IC50

Potency assay (off target):

In BROMOscan assay, testing 19 bromodomains, only CBP/EP300 was affected at < 1 uM; BRD4 KD > 20 uM (by ITC)

Probe Selectivity in Vitro:

Not measured

In cell validation

On target activity in cells

Potency assay (cells):

We performed single cell transcriptional profiling on the Fluidigm microfluidic platform (macrophages) and Affymetrix microarrays (neurons) at a single dose (1 uM). Transcriptional changes in macrophages phenocopy CBP knockdown with siRNA but not BRD4 knockdown. PF-CBP1 modulates the expression of genes that are known targets for CBP in neurons.

Target engagement assay (cells):

Indirect, gene expression profiling described above.

Toxicity

Cytoxicity assay:

Yes

Notes on cytotoxicity:

None detected in macrophages with up to 30 uM PF-CBP1, using Cell Titer Glo assay; in THLE cells (immortilied human liver epithelial cells), IC50=23.7 uM and in HepG2, IC50=35.9 uM in the same assay.

Primary Reference

Reference (doi):

10.1016/j.chembiol.2015.10.013 10.1021/acs.jmedchem.6b01022

Reference (PMID):

26670081 27682507

Endorsed probe

The Chemical Probes Portal endorses this compound as chemical probe for use in cells.

SAB Rating

Rating for use in Cells

3 review(s)

Rating for use in Model Organisms

no rating

SAB Members

SAB 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.

Mar 28 2017 - 9:51pm

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.

Apr 7 2017 - 1:45pm

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.

Jul 27 2017 - 11:39am

PF-CBP1

Probe Availability

Probe Information

Target Details

CREB binding protein, CBP, KAT3A, RSTS, RSTS1, E1A binding protein p300, KAT3B, RSTS2, p300

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

Toxicity

Primary Reference

Supporting Organizations

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PF-CBP1

Probe Availability

Probe Information

Target Details

CREB binding protein, CBP, KAT3A, RSTS, RSTS1, E1A binding protein p300, KAT3B, RSTS2, p300

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

Toxicity

Primary Reference

Supporting Organizations

Interested in supporting the portal?