E-3330

E-3330 - Names and Identifiers

Name	(E)-2-((4,5-dimethoxy-2-methyl-3,6-dioxocyclohexa-1,4-dien-1-yl)methylene)undecanoic acid
Synonyms	E3330 E 3330 E-3330 APX3330 CS-1756 APX 3330 (E)-2-((4,5-dimethoxy-2-methyl-3,6-dioxocyclohexa-1,4-dien-1-yl)methylene)undecanoic acid (2E)-2-[(4,5-Dimethoxy-2-methyl-3,6-dioxo-1,4-cyclohexadien-1-yl)methylene]-undecanoic acid Undecanoic acid, 2-[(4,5-dimethoxy-2-methyl-3,6-dioxo-1,4-cyclohexadien-1-yl)methylene]-, (2E)- (2E)-2-[(4,5-dimethoxy-2-methyl-3,6-dioxocyclohexa-1,4-dien-1-yl)methylidene]undecanoic acid E3330
CAS	136164-66-4
EINECS	604-604-1

E-3330 - Physico-chemical Properties

Molecular Formula	C21H30O6
Molar Mass	378.46
Density	1.13±0.1 g/cm3(Predicted)
Melting Point	56-57 °C
Boling Point	542.2±50.0 °C(Predicted)
Solubility	DMSO: >20mg/mL
Appearance	powder
Color	red to orange
pKa	4.29±0.19(Predicted)
Storage Condition	2-8°C
Use	E3330 is a potent and selective inhibitor of AP endonuclease 1 redox domain.E3330 significantly reduces the growth of human pancreatic cancer cells in vitro and inhibits pancreatic cancer cell migration. E3330 blocks tnf-α-induced activation of IL-8 production in liver cancer cell lines. E3330 inhibits the growth of tumor endothelium and endothelial progenitor cells: therapeutic implications in tumor angiogenesis.
Target	Ape-1, Ref-1
In vitro study	In vitro, E3330 affects hemangioblast development by inhibiting Ape1 redox activity. E3330 inhibits the growth of human pancreatic cancer cell lines PANC1,XPA1,MIAPACA,BxPC3, and pk9. In PANC1 cells, E3330 also promotes the end of the cell cycle, inhibits the DNA binding activity of HIF-1α and the migration of pancreatic cancer cells. In adhh6 cells, E3330 prevents the functional activity of NF-κB by altering the Subcellular transport of APE1 and by blocking the redox-mediated activation of NF-κB, decreased TNF-α and FAs accumulation induced expression by IL-6 and IL-8.
In vivo study	In mice with endotoxin-mediated hepatitis, E3330 (300 mg/kg, p.o.) attenuated the increase in plasma tumor necrosis factor activity and protected mice from liver injury. In a rat model, E3330 (100 mg/kg, p.o.) also protects rats from endotoxin and galactose-induced liver injury.

E-3330 - Reference

Reference

1: Cesaratto L, Codarin E, Vascotto C, Leonardi A, Kelley MR, Tiribelli C, Tell G. Specific inhibition of the redox activity of ape1/ref-1 by e3330 blocks tnf-α-induced activation of IL-8 production in liver cancer cell lines. PLoS One. 2013 Aug 15;8(8):e70909. doi: 10.1371/journal.pone.0070909. eCollection 2013. PubMed PMID: 23967134; PubMed Central PMCID: PMC3744539.
2: Kelley MR, Luo M, Reed A, Su D, Delaplane S, Borch RF, Nyland RL 2nd, Gross ML, Georgiadis MM. Functional analysis of novel analogues of E3330 that block the redox signaling activity of the multifunctional AP endonuclease/redox signaling enzyme APE1/Ref-1. Antioxid Redox Signal. 2011 Apr 15;14(8):1387-401. doi: 10.1089/ars.2010.3410. Epub 2011 Jan 4. PubMed PMID: 20874257; PubMed Central PMCID: PMC3061197.
3: Zou GM, Karikari C, Kabe Y, Handa H, Anders RA, Maitra A. The Ape-1/Ref-1 redox antagonist E3330 inhibits the growth of tumor endothelium and endothelial progenitor cells: therapeutic implications in tumor angiogenesis. J Cell Physiol. 2009 Apr;219(1):209-18. doi: 10.1002/jcp.21666. PubMed PMID: 19097035.
4: Zou GM, Maitra A. Small-molecule inhibitor of the AP endonuclease 1/REF-1 E3330 inhibits pancreatic cancer cell growth and migration. Mol Cancer Ther. 2008 Jul;7(7):2012-21. doi: 10.1158/1535-7163.MCT-08-0113. PubMed PMID: 18645011; PubMed Central PMCID: PMC3569736.
5: Saitou Y, Shiraki K, Yamanaka T, Miyashita K, Inoue T, Yamanaka Y, Yamaguchi Y, Enokimura N, Yamamoto N, Itou K, Sugimoto K, Nakano T. Augmentat