WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H205882
CAS#: 1140964-99-3
Description: Stenoparib, also known as E7449 and 2X-121, is an orally available small molecule inhibitor of the nuclear enzymes poly (ADP-ribose) polymerase (PARP) 1 and 2, with potential antineoplastic activity. Upon administration, E7449 selectively binds to PARP 1 and 2, thereby preventing the repair of damaged DNA via the base excision repair (BER) pathway. This agent enhances the accumulation of single and double strand DNA breaks and promotes genomic instability eventually leading to apoptosis. PARP 1/2 inhibitor E7449 may enhance the cytotoxicity of DNA-damaging agents and of radiotherapy. PARP catalyzes post-translational ADP-ribosylation of nuclear proteins that signal and recruit other proteins to repair damaged DNA.
Hodoodo Cat#: H205882
Name: Stenoparib
CAS#: 1140964-99-3
Chemical Formula: C18H15N5O
Exact Mass: 317.13
Molecular Weight: 317.340
Elemental Analysis: C, 68.13; H, 4.76; N, 22.07; O, 5.04
Synonym: E7449; E 7449; E-7449; 2X-121; 2X 121; 2X121; Stenoparib
IUPAC/Chemical Name: 8-(isoindolin-2-ylmethyl)-2H-pyridazino[3,4,5-de]quinazolin-3(9H)-one
InChi Key: JLFSBHQQXIAQEC-UHFFFAOYSA-N
InChi Code: InChI=1S/C18H15N5O/c24-18-13-6-3-7-14-16(13)17(21-22-18)20-15(19-14)10-23-8-11-4-1-2-5-12(11)9-23/h1-7H,8-10H2,(H,22,24)(H,19,20,21)
SMILES Code: O=C1NN=C(N2)C3=C(C=CC=C31)N=C2CN(C4)CC5=C4C=CC=C5
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info:
Biological target: | E7449 is a PARP1 and PARP2 inhibitor and also inhibits TNKS1 and TNKS2, with IC50s of 2.0, 1.0, ∼50 and ∼50 nM for PARP1, PARP2, TNKS1 and TNKS2, respectively. |
In vitro activity: | In wild type DT40 cells E7449 inhibited cell proliferation in a 2 day assay with an IC50 value of 3.2 μmol/L; this value was used for normalization of E7449 IC50 values obtained in mutant cells (Figure 1D, see Supplementary Figure 3 for representative IC50 curves). Reference: Oncotarget. 2015 Dec 1; 6(38): 41307–41323. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4747407/ |
In vivo activity: | In an in vivo subcutaneous MDA-MB-436 xenograft model, administration of E7449 at 30 or 100 mg/kg once daily for 28 days resulted in statistically significant antitumor activity (Figure 3B). A dose response was observed, with greater tumor growth inhibition at the higher 100 mg/kg dose. Reference: Oncotarget. 2015 Dec 1; 6(38): 41307–41323. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4747407/ |
Solvent | Max Conc. mg/mL | Max Conc. mM | |
---|---|---|---|
Solubility | |||
DMSO | 0.2 | 0.63 |
The following data is based on the product molecular weight 317.34 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
---|---|---|---|
1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
Formulation protocol: | 1. McGonigle S, Chen Z, Wu J, Chang P, Kolber-Simonds D, Ackermann K, Twine NC, Shie JL, Miu JT, Huang KC, Moniz GA, Nomoto K. E7449: A dual inhibitor of PARP1/2 and tankyrase1/2 inhibits growth of DNA repair deficient tumors and antagonizes Wnt signaling. Oncotarget. 2015 Dec 1;6(38):41307-23. doi: 10.18632/oncotarget.5846. PMID: 26513298; PMCID: PMC4747407. |
In vitro protocol: | 1. McGonigle S, Chen Z, Wu J, Chang P, Kolber-Simonds D, Ackermann K, Twine NC, Shie JL, Miu JT, Huang KC, Moniz GA, Nomoto K. E7449: A dual inhibitor of PARP1/2 and tankyrase1/2 inhibits growth of DNA repair deficient tumors and antagonizes Wnt signaling. Oncotarget. 2015 Dec 1;6(38):41307-23. doi: 10.18632/oncotarget.5846. PMID: 26513298; PMCID: PMC4747407. |
In vivo protocol: | 1. McGonigle S, Chen Z, Wu J, Chang P, Kolber-Simonds D, Ackermann K, Twine NC, Shie JL, Miu JT, Huang KC, Moniz GA, Nomoto K. E7449: A dual inhibitor of PARP1/2 and tankyrase1/2 inhibits growth of DNA repair deficient tumors and antagonizes Wnt signaling. Oncotarget. 2015 Dec 1;6(38):41307-23. doi: 10.18632/oncotarget.5846. PMID: 26513298; PMCID: PMC4747407. |
1: Laurance J. Neurologists appeal to health secretary over withdrawal of drug for MS patients. BMJ. 2012 Nov 2;345:e7449. doi: 10.1136/bmj.e7449. PubMed PMID: 23125160.
2: Gilmore S, Hofmann-Wellenhof R, Muir J, Soyer HP. Lacunarity analysis: a promising method for the automated assessment of melanocytic naevi and melanoma. PLoS One. 2009 Oct 13;4(10):e7449. doi: 10.1371/journal.pone.0007449. PubMed PMID: 19823688; PubMed Central PMCID: PMC2758593.