E7449

Reagent Authentication Certificate:

Chemical Probes Portal E7449.pdf

Protein target name:

PARP1, PARP2, TNKS, TNKS2

Mechanism of action:

Inhibitor

Recommended Concentration for use in cells:

Up to 1 uM

Probe Availability

MedChem Express (1140964-99-3)

Probe Information

Target and Probe Information

Target Details

Target class:

ADPRT, ADPRT 1, ADPRT1, ARTD1, PARP, PARP-1, PPOL, pADPRT-1, ADPRT2, ADPRTL2, ADPRTL3, ARTD2, PARP-2, pADPRT-2, TIN1; ARTD5; PARPL; TINF1; TNKS1; pART5; PARP5A; PARP-5a, ARTD6, PARP-5b, PARP-5c, PARP5B, PARP5C, TANK2, TNKL, pART6

Probe Details

Chemical Probes Portal ID:

CPP597

Probe alias:

UNII-9X5A2QIA7C; 9X5A2QIA7C, CS-3479; HY-12418

PubChem CID:

25267262

ChEMBL ID:

CHEMBL3644587

SMILES string:

C1C2=CC=CC=C2CN1CC3=NC4=CC=CC5=C4C(=N3)NNC5=O

InChi Key:

JLFSBHQQXIAQEC-UHFFFAOYSA-N

Orthogonal probe:

OlaparibTalazoparibAZ6102

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

IC50

PARP1 1.0 nM, PARP2 1.2 nM, TNKS 115 nM

Potency assay:

Trevigen ELISA assay

Off target activity

Potency assay (off target):

In PARylation assays with human PARPs, E7449 was only active against PARP1, PARP2, TNKS, and TNKS2.

Probe Selectivity in Vitro:

Not available

In cell validation

On target activity in cells

Potency assay (cells):

DT40 cells lacking PARP proteins or other DNA repair proteins are resistant to E7449. In SW480 cells, E7449 dose-dependently stabilized axin2, TNKS, and TNKS2, and decreased beta-catenin activation.

Target engagement assay (cells):

Not available

In vivo validation

Organism:

mouse

Dose:

30-100 mg/kg

Organ of Interest

Organ (O):

hair follicle, tumor xenograft

Primary Reference

Reference (doi):

10.18632/oncotarget.5846

Reference (PMID):

26513298

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

E7449 is a potent inhibitor of PARP1 and PARP2 (IC50: 1-2 nM), which, unlike many other PARP inhibitors also has significant activity against Tankyrases 1 and 2 (ca. 100 nM). It has been extensively characterized in cellular and in vivo models and is a good probe for the study of PARP1, PARP2, TNKS1 and TNKS2, but should only be used when this pharmacological profile is required. The lack of broader selectivity data should also be noted.

Sep 12 2016 - 7:06pm

Users should be aware that this compound will trap PARP on DNA, a property not all PARP inhibitors possess. Compounds are reported to have good selelctivity over PARP3 and PARP6-16, with PARP4 described as having a minimal signal

Oct 1 2016 - 3:06pm

The probe appears to be selective against other PARPs and the on-target pharmacology is well-characterized, but there are no data regarding broader off-target profiling - this should be better understood prior to use. The value of 'dual' inhibition would appear to be for in vivo studies, since selective PARP1/2 and tankyrase inhibitors already exist (so allowing titrations in cells).

Jan 4 2017 - 11:42am

The inhibitor E7449 should be used against the target proteins PARP1, PARP2, TNKS1 and TNKS2 in a combination therapy. Several relevant examples are presented, which should encourage further exploration for either additional combination therapies.

Aug 3 2017 - 3:44pm

E7449

Probe Availability

Probe Information

Target Details

ADPRT, ADPRT 1, ADPRT1, ARTD1, PARP, PARP-1, PPOL, pADPRT-1, ADPRT2, ADPRTL2, ADPRTL3, ARTD2, PARP-2, pADPRT-2, TIN1; ARTD5; PARPL; TINF1; TNKS1; pART5; PARP5A; PARP-5a, ARTD6, PARP-5b, PARP-5c, PARP5B, PARP5C, TANK2, TNKL, pART6

Probe Details

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

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E7449

Probe Availability

Probe Information

Target Details

ADPRT, ADPRT 1, ADPRT1, ARTD1, PARP, PARP-1, PPOL, pADPRT-1, ADPRT2, ADPRTL2, ADPRTL3, ARTD2, PARP-2, pADPRT-2, TIN1; ARTD5; PARPL; TINF1; TNKS1; pART5; PARP5A; PARP-5a, ARTD6, PARP-5b, PARP-5c, PARP5B, PARP5C, TANK2, TNKL, pART6

Probe Details

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

Interested in supporting the portal?