APX3330 sodium | CAS#136164-66-4 | APE1 inhibitor

MedKoo Cat#: 406611 | Name: APX3330 sodium

Description:

WARNING: This product is for research use only, not for human or veterinary use.

APX3330, also known as E3330, is a potent and orally active APE1/Ref-1 redox inhibitor with potential anti-angiogenic and antineoplastic activities. APX3330 selectively targets and binds to APE1/Ref-1. This inhibits the redox-dependent signaling activity of APE1/Ref-1, by preventing the reduction and activation of numerous APE1/Ref-1-dependent oncogenic transcription factors (TFs), such as nuclear factor kappa B (NF-kB), AP-1, STAT3, p53, NRF2 and HIF-1alpha, that are involved in signaling, cell proliferation, tumor progression and survival of cancer cells.

Chemical Structure

APX3330 sodium

CAS#APX3330 sodium

Theoretical Analysis

MedKoo Cat#: 406611

Name: APX3330 sodium

CAS#: APX3330 sodium

Chemical Formula: C21H29NaO6

Exact Mass: 0.0000

Molecular Weight: 400.45

Elemental Analysis: C, 62.99; H, 7.30; Na, 5.74; O, 23.97

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Related CAS #

APX3330 sodium 136164-66-4 (free acid)

Synonym

APX3330; APX-3330; APX 3330; E3330; E-3330; E 3330;

IUPAC/Chemical Name

sodium (E)-2-((4,5-dimethoxy-2-methyl-3,6-dioxocyclohexa-1,4-dien-1-yl)methylene)undecanoate

InChi Key

CDVZZRRHMGOEEP-GVYCEHEKSA-M

InChi Code

InChI=1S/C21H30O6.Na/c1-5-6-7-8-9-10-11-12-15(21(24)25)13-16-14(2)17(22)19(26-3)20(27-4)18(16)23;/h13H,5-12H2,1-4H3,(H,24,25);/q;+1/p-1/b15-13+;

SMILES Code

CCCCCCCCC/C(C([O-])=O)=C\C1=C(C)C(C(OC)=C(OC)C1=O)=O.[Na+]

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

Product Data

Product Data

Instruction

View handling instruction

Biological target:

E3330 (APX-3330) is an AP endonuclease 1 (APE1; REF-1) inhibitor, which suppresses NF-κB DNA-binding activity.

In vitro activity:

To investigate the effect of E3330 on TNF-α-induced IL-8 expression, JHH6 cells were pre-treated with 100 µM E3330 for 4 h before exposure to TNF-α. As shown in figure 4, pre-treatment with E3330 significantly decreased TNF-α-induced IL-8 expression in terms of both endogenous mRNA transcription (Fig. 4A) and protein production (Fig. 4B). These data point to a potential use of E3330 to reduce the inflammatory processes in liver diseases such as those associated with NASH. Reference: PLoS One. 2013; 8(8): e70909. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3744539/

In vivo activity:

Interestingly, E3330 partially prevented pain sensitization that occurs between day zero and day 4 (CFA+E3330, 117.31 ± 8.44 and 96.93 ± 3.92 at days 0 and 4, respectively, p < .05). On day 4, E3330 application significantly increased the paw withdrawal threshold (pain alleviation) in CFA rats as compared to the CFA rats injected with saline (CFA+Saline vs CFA+E3330 at day 4, p < .001) (Fig. 7). Accordingly, the CFA+Saline group exhibited significantly higher pain sensitivity with respect to CFA+E3330 rats (p < .001, 118.60 ± 6.64 and 66.75 ± 7.59 at days zero and 4, respectively). These results demonstrate that APE1 redox function is implicated, at least partially, in pain pathway. Reference: Exp Neurol. 2018 Sep;307:1-11. doi: 10.1016/j.expneurol.2018.05.014. https://pubmed.ncbi.nlm.nih.gov/29772245/

	Solvent	mg/mL	mM
Solubility
	Ethanol	75.0	198.17

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 400.45 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. 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. PMID: 23967134; PMCID: PMC3744539. 2. 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. PMID: 19097035. 3. Zaky A, Bouali-Benazzouz R, Favereaux A, Tell G, Landry M. APE1/Ref-1 redox function contributes to inflammatory pain sensitization. Exp Neurol. 2018 Sep;307:1-11. doi: 10.1016/j.expneurol.2018.05.014. Epub 2018 May 14. PMID: 29772245. 4. Li Y, Liu X, Zhou T, Kelley MR, Edwards PA, Gao H, Qiao X. Suppression of choroidal neovascularization through inhibition of APE1/Ref-1 redox activity. Invest Ophthalmol Vis Sci. 2014 Jun 26;55(7):4461-9. doi: 10.1167/iovs.14-14451. PMID: 24970265; PMCID: PMC4106251.

In vitro protocol:

In vivo protocol:

1. Zaky A, Bouali-Benazzouz R, Favereaux A, Tell G, Landry M. APE1/Ref-1 redox function contributes to inflammatory pain sensitization. Exp Neurol. 2018 Sep;307:1-11. doi: 10.1016/j.expneurol.2018.05.014. Epub 2018 May 14. PMID: 29772245. 2. Li Y, Liu X, Zhou T, Kelley MR, Edwards PA, Gao H, Qiao X. Suppression of choroidal neovascularization through inhibition of APE1/Ref-1 redox activity. Invest Ophthalmol Vis Sci. 2014 Jun 26;55(7):4461-9. doi: 10.1167/iovs.14-14451. PMID: 24970265; PMCID: PMC4106251.

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. Augmentation of tumor necrosis factor family-induced apoptosis by E3330 in human hepatocellular carcinoma cell lines via inhibition of NF kappa B. World J Gastroenterol. 2005 Oct 28;11(40):6258-61. PubMed PMID: 16419152. 6: Hiramoto M, Shimizu N, Sugimoto K, Tang J, Kawakami Y, Ito M, Aizawa S, Tanaka H, Makino I, Handa H. Nuclear targeted suppression of NF-kappa B activity by the novel quinone derivative E3330. J Immunol. 1998 Jan 15;160(2):810-9. PubMed PMID: 9551916. 7: Uetsuka K, Suzuki M, Kai C, Goto N. Protective effects of a novel quinone derivative, E3330, on mouse hepatitis virus (MHV)-induced chronic hepatitis in athymic nude mice. Exp Anim. 1997 Jul;46(3):219-23. PubMed PMID: 9250483. 8: Goto M, Yamada K, Katayama K, Tanaka I. Inhibitory effect of E3330, a novel quinone derivative able to suppress tumor necrosis factor-alpha generation, on activation of nuclear factor-kappa B. Mol Pharmacol. 1996 May;49(5):860-73. PubMed PMID: 8622636. 9: Tanaka H, Makino Y, Hiramoto M, Handa H, Makino I. Potentiation of glucocorticoid-mediated gene expression by the novel benzoquinone derivative (2E)-3-[5-(2,3-dimethoxy-o-methyl-1, 4-benzoquinoyl)]-2-nonyl-2-propenoic acid (E3330). Eur J Pharmacol. 1995 Oct 15;291(2):121-7. PubMed PMID: 8566161. 10: Wasaki S, Sakaida I, Nagatomi A, Matsumura Y, Yasunaga M, Okita K. The effect of E3330 on active oxygen generation by isolated hepatic macrophages in rats. J Gastroenterol. 1995 Apr;30(2):273-4. PubMed PMID: 7773361.