Catalog Number
ACM1140964993
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
Molecular Formula
C18H15N5O
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
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
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).
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