E-7449


Catalog No. size PriceQuantity
M6501-2 2mg solid $111
M6501-10 10mg solid $441

Description

Cas:1140964-99-3

Product Information:

E-7449, also known as 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.

 

Chemical Formula: C18H15N5O

 

Exact Mass: 317.12766

 

Molecular Weight: 317.34

 

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

 

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

 

 

Technical Data:

 

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

 

In Vitro:

E7449 is a potent 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, using 32P-NAD+ as substrate. E7449 shows no obvious inhibiotry effects on PARP3 or PARPs 6-16. E7449 traps PARP1 onto damaged DNA, and affects DNA repair pathways beyond homologous recombination (HR). E7449 most potnetly suppresses cells deficient in components of the HR pathway (BRCA1 and 2, CtIP, Rad54). E7449 (10 μM) inhibits Wnt signaling in SW480 cells.

 

In Vivo:

E7449 moderately inhibits the growth of tumors at 100 mg/kg, and significantly ehhances the inhibition via 10, 30 and 100 mg/kg oral dosing in combination with temozolomide (TMZ) in the mouse melanoma B16-F10 isograft model. E7449 (30 or 100 mg/kg, p.o.) inhibits PARP, shows anti-tumor activity, and is well-tolerated without any obvious body weight loss or deaths in a BRCA mutant xenograft model. E7449 (30, 100 or 300 mg/kg, p.o.) suppresses re-growth of hair in a dose dependent manner, and blocks Wnt signaling in C57BL/6 mice. E7449 (100 mg/kg, p.o.) combined with MEK inhibitor exhibits antitumor activity in a Wnt1 subcutaneous model (mammary tumors initially isolated from Wnt1 (int-1) transgenic mice).

 

References

 

  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.

 

  1. 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.

 

Products are for research use only. Not for human use.

 

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