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E7449

Cat. No. M5267
E7449 Structure
Size Price Availability Quantity
5mg USD 133 In stock
10mg USD 233 In stock
25mg USD 445 In stock
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Quality Control
  • Current batch:
  • Purity >99%
  • COA
  • MSDS
Biological Activity

In vitro: E7449 inhibits PARP enzymatic activity and additionally traps PARP1 onto damaged DNA; a mechanism previously shown to augment cytotoxicity. E7449 inhibits Wnt/β-catenin signaling in colon cancer cell lines, likely through TNKS inhibition. E7449 stabilizes axin and TNKS proteins resulting in β-catenin de-stabilization and significantly alters expression of Wnt target genes. E7449 inhibits TNKS1 and 2 (PARP5a and 5b) with IC50 values of 50-100 nmol/L. Significant inhibitory activity is not observed for PARP3 or PARPs 6-16 (PARP9 and 13 lack activity and PARP4 had minimal signal. In vivo: Chemotherapy is potentiated by E7449 and single agent has significant antitumor activity in BRCA-deficient xenografts. E7449 lacks single agent antitumor activity in vivo. E7449 antitumor activity is increased through combination with MEK inhibition. Treatment with E7449 at 30 or 100 mg/kg in xenografts is well-tolerated without any significant body weight loss or deaths. Treatment with E7449 at 100 mg/kg resulted in significant PARP inhibition that is sustained for at least 12 hours and recovered to basal levels within 24 h.

Protocol
Cell Experiment
Cell lines Human breast cancer cell lines, HCC1143, HCC70, HCC1806, MDA-MB-436, T47D, MDA-MB-157, MDA-MB-231, MDA-MB-468, MDA-MB-453, BT-20 and Hs578T
Preparation method For proliferation assays cells are plated at low density in 96 well plates. E7449 is added at various concentrations and plates incubated for a total of 8 days; compound and medium are replenished on day 4. Cell growth is assessed.
Concentrations
Incubation time 8 days
Animal Experiment
Animal models C57BL/6 mice
Formulation 0.5% methyl cellulose in water
Dosages 30, 100 or 300 mg/kg
Administration oral administration
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information
Molecular Weight 317.34
Formula C18H15N5O
CAS Number 1140964-99-3
Purity >99%
Solubility 4 mg/mL in DMSO
Storage at -20°C
References

E7449: A dual inhibitor of PARP1/2 and tankyrase1/2 inhibits growth of DNA repair deficient tumors and antagonizes Wnt signaling.
McGonigle S, et al. Oncotarget. 2015 Dec 1;6(38):41307-23. PMID: 26513298.

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  Catalog
Abmole Inhibitor Catalog 2017




Keywords: E7449 supplier, PARP, inhibitors

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