Stenoparib (E7449)

Catalog No.S8419 Synonyms: 2X-121, MGI25036

For research use only.

Stenoparib (E7449, 2X-121, MGI25036) is an orally bioavailable, brain penetrable, small molecule dual inhibitor of PARP1/2 and also inhibits PARP5a/5b, otherwise known as tankyrase1 and 2 (TNKS1/2), important regulators of canonical Wnt/β-catenin signaling. It has IC50 values of 1.0 and 1.2 nM for PARP1 and 2, respectively.

Stenoparib (E7449) Chemical Structure

CAS No. 1140964-99-3

Selleck's Stenoparib (E7449) has been cited by 2 Publications

Purity & Quality Control

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Biological Activity

Description Stenoparib (E7449, 2X-121, MGI25036) is an orally bioavailable, brain penetrable, small molecule dual inhibitor of PARP1/2 and also inhibits PARP5a/5b, otherwise known as tankyrase1 and 2 (TNKS1/2), important regulators of canonical Wnt/β-catenin signaling. It has IC50 values of 1.0 and 1.2 nM for PARP1 and 2, respectively.
Targets
PARP1 [1]
()
PARP2 [1]
1 nM 1.2 nM
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)[1].

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[1].

Protocol (from reference)

Cell Research:[1]
  • 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
  • Concentrations: --
  • Incubation Time: 8 days
  • 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.
Animal Research:[1]
  • Animal Models: C57BL/6 mice
  • Dosages: 30, 100 or 300 mg/kg
  • Administration: oral administration

Solubility (25°C)

In vitro

DMSO 4 mg/mL warmed
(12.6 mM)
Water Insoluble
Ethanol Insoluble

Chemical Information

Molecular Weight 317.34
Formula

C18H15N5O

CAS No. 1140964-99-3
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles C1C2=CC=CC=C2CN1CC3=NC4=NNC(=O)C5=C4C(=CC=C5)N3

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Molarity Calculator

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Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT02396433 Withdrawn Drug: Carboplatin|Drug: Eribulin|Drug: E7449 Cancer of the Breast The University of Texas Health Science Center at San Antonio April 2015 Phase 1|Phase 2

(data from https://clinicaltrials.gov, updated on 2022-01-17)

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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