CP-724714

Reagent Authentication Certificate:

Chemical Probes Portal CP-724714.pdf

Protein target name:

ERBB2

Mechanism of action:

Inhibitor

Recommended Concentration for use in cells:

50 nM - 10 uM

Probe Availability

MedChem Express (383432-38-0)

Tocris (383432-38-0)

Abcam (383432-38-0)

MilliporeSigma (383432-38-0)

Cayman (383432-38-0)

Probe Information

Target and Probe Information

Target Details

Target class:

Protein kinase

Subclass:

RTK

HUGO ID:

HGNC:3430

Entrez gene ID:

2064

UNIPROT ID:

P04626

Target alias:

CD340, HER-2, HER-2/neu, HER2, MLN 19, NEU, NGL, TKR1

Probe Details

Chemical Probes Portal ID:

CPP125

Probe alias:

CP 724714

PubChem CID:

9874913

ChEMBL ID:

CHEMBL483321

SMILES string:

CC1=NC=C(C=C1)OC2=C(C=C(C=C2)NC3=NC=NC4=C3C=C(C=C4)/C=C/CNC(=O)COC)C

InChi Key:

LLVZBTWPGQVVLW-SNAWJCMRSA-N

PAINs evaluation:

PAINs free

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

IC50

3 nM

Potency assay:

In vitro kinase assay with intracellular domain

Off target activity

Potency (off target):

IC50

Off target protein and potency:

EGFR 6400 nM

Potency assay (off target):

In vitro kinase assay on intracellular domain >1,000-fold selective for ERBB2 over IGF1R, PDGFRbeta, VEGFR2, ABL, SRC, MET, JUN, JNK2, JNK3, ZAP-70, CDK2, CDK5.

In cell validation

On target activity in cells

Potency in cells:

IC50

32 nM

Potency assay (cells):

Protein substrate phosphorylation in transfected NIH 3T3 cells

Target engagement assay (cells):

Indirect: inhibition of protein substrate phosphorylation

Off target activity in cells

Potency assay, off target (cells):

Selective for ERBB2 over EGFR in cells

In vivo validation

Organism:

CD1 nu/nu mice

Dose:

2.5 mg/kg

Route of delivery:

Oral

Organ of Interest

Organ (O):

xenograft

Target engagement assay:

Indirect: inhibition of protein substrate phosphorylation detected by ex vivo ELISA in xenograft tumor tissue

Primary Reference

Reference (doi):

10.1158/0008-5472.CAN-06-3559

Reference (PMID):

17942920

External Resources

Available data:

GDSC1

Endorsed probe

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

SAB Rating

Rating for use in Cells

3 review(s)

Rating for use in Model Organisms

3 review(s)

SAB Members

SAB Comments

CP-724714 is available commercially through several vendors, and the scientific community has been using the agent largely as a cellular probe for selective and potent inhibition of HER2/ERBB2. It has an IC50 of 10 nM, and is >640-fold selective against EGFR, InsR, IRG-1R, PDGFR, VEGFR2, ABL, SRC, c-MET, etc. in cell-free assays. The published information regarding the use of CP-724714 in various cell lines and in animals makes this a valuable probe for cellular assays.

Jun 29 2016 - 8:05pm

If I were going to use this compound in my studies, I would also likely include Mubritinib (TAK-165), which is a potent inhibitor of HER2/ErbB2 with IC50 of 6 nM in BT-474 cells and shows no activity against EGFR, FGFR, PDGFR, JAK1, SEC or BLK in BT-474 cell lines.

Aug 17 2016 - 7:47pm

CP-724714 is a potent inhibitor of ERBB2 kinase in both cell-free (IC50=10 nM) and cellular (IC50=32 nM) assays with good selectivity over EGFR kinase (>500-fold) and other representative kinases (>1000-fold). Published data supports the use of CP-724714 in both cellular and mouse models at reasonable concentrations and doses. A 25 mg/kg oral dose in mouse is rapidly absorbed and achieved plasma levels of 12.5 ug/mL at 30 min.

Oct 18 2016 - 3:13pm

CP-724714 is a selective, cell-permeable chemical probe for ERBB2, with minimal collateral engagement to other tyrosine kinases. It has 10 nM potency with solid cellular and biophysical characterization. It has been validated in a number of cancer cell lineages, supporting its general use as a chemical probe for cellular applications. Cellular studies should be performed with >50 nM CP-724714.

Jan 23 2017 - 1:35pm

CP-724714

Probe Availability

Probe Information

Target Details

CD340, HER-2, HER-2/neu, HER2, MLN 19, NEU, NGL, TKR1

Probe Details

In vitro validation

In cell validation

In vivo validation

Primary Reference

External Resources

Supporting Organizations

Interested in supporting the portal?

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CP-724714

Probe Availability

Probe Information

Target Details

CD340, HER-2, HER-2/neu, HER2, MLN 19, NEU, NGL, TKR1

Probe Details

In vitro validation

In cell validation

In vivo validation

Primary Reference

External Resources

Supporting Organizations

Interested in supporting the portal?