I-CBP112

Reagent Authentication Certificate:

Chemical Probes Portal ICBP112.pdf

Protein target name:

CREBBP, EP300

Mechanism of action:

Antagonizes interaction with acetylated lysine

Recommended Concentration for use in cells:

Up to 1 uM

Probe Availability

Tocris (ICBP112)

MedChem Express (1640282-31-0)

MilliporeSigma (ICBP112)

Cayman (I-CBP112 hydrochloride)

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:

CBP, KAT3A, RSTS, KAT3B, RSTS2, p300

Probe Details

Chemical Probes Portal ID:

CPP71

Probe alias:

GTPL8236

PubChem CID:

90488984

SMILES string:

CCC(=O)N1CCOC2=C(C1)C=C(C=C2OC[C@H]3CCCN(C3)C)C4=CC(=C(C=C4)OC)OC

InChi Key:

YKNAKDFZAWQEEO-IBGZPJMESA-N

PAINs evaluation:

PAINs free

Physico-chemical properties

Solubility - preferred solvent:

DMSO

Solubility - concentration:

100 mM

Storage Recommendations

Storage (dry powder):

2 years -20 oC

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

CREBBP 151 nM, EP300 167 nM

Potency assay:

ITC and also by biolayer interferometry I-CBP112 displaced acetylated lysine peptides from CBP with an IC50 = 170 nM.

PDB ID for probe-target interaction (3D structure):

4NR6

Off target activity

Potency (off target):

Off target protein and potency:

BRD4 (1) 5.6 uM (2) 20 uM

Potency assay (off target):

ITC, and using biointerferometry, I-CBP112 did not bind to any additional of 40 Bromodomains tested.

Probe Selectivity in Vitro:

Minimal activity against 104 proteins (nuclear receptors, ion channels, kinases, proteases, and phosphodiesterases). I-CBP112 interacted weakly with two GPCRs: alpha1A and 5HT1.

In cell validation

On target activity in cells

Potency in cells:

IC50

600 nM

Potency assay (cells):

In cells, I-CBP112 interfered with CBP interaction with acetylated lysine-containing proteins in FRAP and BRET assays.

Target engagement assay (cells):

Indirect: FRAP and BRET assays

In vivo validation

Organism:

mice

Dose:

3 mg/mL

Route of delivery:

Intraperitoneal

Plasma half life:

0.6 hr

Cmax:

590 ng/mL

Organ of Interest

Organ (O):

bone marrow transplant with MLL-AF9 leukemia cells

Primary Reference

Reference (doi):

10.1158/0008-5472.CAN-15-0236

Reference (PMID):

26552700

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

3 review(s)

SAB Members

SAB Comments

Bromodomain probe with selectivity for CBP/p300 outside of the BET family. This probe is able to displace p300 and CBP from acetylated proteins at low micromolar concentrations. Use at concentrations 1,000 - 5,000 nM appropriate in cellular assays. At concentrations higher than this range, 'off targeting' of BRD4 may be observed.

Apr 5 2017 - 4:27pm

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.

Apr 7 2017 - 1:51pm

I-CBP112

Probe Availability

Probe Information

Target Details

CBP, KAT3A, RSTS, KAT3B, RSTS2, p300

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

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I-CBP112

Probe Availability

Probe Information

Target Details

CBP, KAT3A, RSTS, KAT3B, RSTS2, p300

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

Interested in supporting the portal?