Stenoparib

• CAS: 1140964-99-3
• Catalog Number: ACM1140964993
• Category: Inhibitors
• Molecular Weight: 317.34
• Molecular Formula: C18H15N5O
• 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.
• Synonyms: E7449; E 7449; E-7449; 2X-121; 2X 121; 2X121; Stenoparib
• IUPAC Name: 8-(isoindolin-2-ylmethyl)-2H-pyridazino[3,4,5-de]quinazolin-3(9H)-one
• Canonical SMILES: O=C1NN=C(N2)C3=C(C=CC=C31)N=C2CN(C4)CC5=C4C=CC=C5
• InChI: 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)
• InChI Key: JLFSBHQQXIAQEC-UHFFFAOYSA-N
• Solubility: Soluble in DMSO, not in water
• Appearance: Solid powder
• Shelf Life: >2 years if stored properly
• Storage: Dry, dark and at 0-4 °C for short term (days to weeks) or -20 °C for long term (months to years).
• 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.
• Drug Formulation: This drug may be formulated in DMSO
• Elemental Analysis: C, 68.13; H, 4.76; N, 22.07; O, 5.04
• Exact Mass: 317.12766
• HS Tariff Code: 2934.99.9001
• 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/
• Shipping: 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.
• Stock Solution Storage: 0-4 °C for short term (days to weeks), or -20 °C for long term (months).