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E3330 (Synonyms: APX 3330)

Catalog No.GC10620

E3330 is a small-molecule inhibitor of apurinic-apyrimidinic endonuclease/redox effector factor (APE1/Ref-1) redox domain function (IC50, 50 µmol/L).

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E3330 Chemical Structure

Cas No.: 136164-66-4

Size Price Stock Qty
10mM (in 1mL DMSO)
$89.00
In stock
5mg
$107.00
In stock
10mg
$176.00
In stock
50mg
$495.00
In stock
100mg
$719.00
In stock

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Sample solution is provided at 25 µL, 10mM.

Product has been cited by 2 publications

Product Documents

Quality Control & SDS

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Protocol

Cell experiment [1]:

Cell lines

Pancreatic cancer PaCa-2 and Panc-1 cells

Preparation Method

Cells were were maintained at 37 ⊿in 5% CO2 and grown in Dulbecco's Modified Eagle's Medium with 10% cosmic calf serum. PaCa-2 and Panc-1 cells were treated with E3330 for 72 and 48 hours, respectively.

Reaction Conditions

0-135 µM for 48, 72 h

Applications

E3330 was found to effectively slow the growth rate of cells in a dose-dependent manner, with an ED50 of 135 and 87 µmol/L for PaCa-2 and Panc-1, respectively.

Animal experiment [2]:

Animal models

Nonobese diabetic/severe combined immunodeficient mice (NOD/SCID) mice

Preparation Method

PaCa-2 cells (2.5 × 106) in 0.2 mL of DMEM media were implanted s.c. into the right flanks of NOD/SCID mice. E3330 was dissolved in 4% CremophorEL:EtOH (1:1)/saline solution or methylcellulose (0.5%). When tumor volumes were greater than 100 mm3, E3330 was administered orally twice daily, 8 hours apart, at 25 mg/kg for 10 to 12 days (5 days on 2 days off schedule). Tumors were measured biweekly and followed for approximately 6 weeks.

Dosage form

25 mg/kg, orally twice daily, for 10 to 12 days (5 days on 2 days off schedule)

Applications

In contrast to vehicle-control tumors, PaCa-2 xenografts showed a significant tumor growth delay.

References:

[1] : Fishel M L, Jiang Y, Rajeshkumar N V, et al. Impact of APE1/Ref-1 Redox Inhibition on Pancreatic Tumor GrowthAPE1/Ref-1 Redox Inhibition on Pancreatic Tumor Growth[J]. Molecular cancer therapeutics, 2011, 10(9): 1698-1708.

Background

E3330 is a small-molecule inhibitor of apurinic-apyrimidinic endonuclease/redox effector factor (APE1/Ref-1) redox domain function (IC50, 50 µmol/L) [1,2].

E3330(10-30 µM, 72h) inhibits not only the growth but also the migratory abilities of pancreatic cancer cells in vitro [1].The co-incubation of E3330(30 µM, 3 h ) and cisplatin (5-20 µM, 72 h) significantly decreased cell viability compared to cisplatin alone in the human NSCLC cell line H1975 [3]. E3330 treatment prevented the functional activation of NF-κB via the alteration of APE1 subcellular trafficking and reduced IL-6 and IL-8 expression induced by TNF-α [4]. E3330 clearly suppressed secretion of inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin (IL-6) and IL-12 and inflammatory mediators nitric oxide (NO) as well as prostaglandin E2 (PGE2) from the LPS-stimulated RAW264.7 cells [5].

E3330 (10-100 mg/kg, oral) treatment 1 hr after galactosamine challenge attenuated the liver injury. E3330 was effective when administered p.o. 6 or 12 hr after galactosamine challenge in the galactosamine-induced hepatitis model in F344 rats [6]. The injection of TNF in combination with galactosamine resulted in severe liver injury. Oral pretreatment with 100 and 300 mg/kg of E3330 30 min prior to the injection of galactosamine/TNF significantly attenuated the increase in plasma L-alanine aminotransferase and L-aspartate aminotransferase activities [7]. The estimated half-life (t1/2) of E3330 was 3.7 hours in mice [2].

References:
[1]. Zou G M, Maitra A. Small-molecule inhibitor of the AP endonuclease 1/REF-1 E3330 inhibits pancreatic cancer cell growth and migration[J]. Molecular cancer therapeutics, 2008, 7(7): 2012-2021.
[2]. Fishel M L, Colvin E S, Luo M, et al. Inhibition of the redox function of APE1/Ref-1 in myeloid leukemia cell lines results in a hypersensitive response to retinoic acid-induced differentiation and apoptosis[J]. Experimental hematology, 2010, 38(12): 1178-1188.
[3]. Manguinhas R, Fernandes A S, Costa J G, et al. Impact of the APE1 redox function inhibitor E3330 in non-small cell lung cancer cells exposed to cisplatin: increased cytotoxicity and impairment of cell migration and invasion[J]. Antioxidants, 2020, 9(6): 550.
[4]. Cesaratto L, Codarin E, Vascotto C, et al. 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[J]. PLoS One, 2013, 8(8): e70909.
[5]. Jedinak A, Dudhgaonkar S, Kelley M R, et al. Apurinic/Apyrimidinic endonuclease 1 regulates inflammatory response in macrophages[J]. Anticancer research, 2011, 31(2): 379-385.
[6]. Nagakawa J, Hirota K, Hishinuma I, et al. Protective effect of E3330, a novel quinone derivative, in galactosamine-induced hepatitis in rats[J]. Journal of Pharmacology and Experimental Therapeutics, 1993, 264(1): 496-500.
[7]. Nagakawa J, Hishinuma I, Hirota K, et al. Protective effects of E3330, a novel quinone derivative, on galactosamine/tumor necrosis factor-α-induced hepatitis in mice[J]. European journal of pharmacology, 1992, 229(1): 63-67.

Chemical Properties

Cas No. 136164-66-4 SDF
Synonyms APX 3330
Chemical Name (E)-2-((4,5-dimethoxy-2-methyl-3,6-dioxocyclohexa-1,4-dien-1-yl)methylene)undecanoic acid
Canonical SMILES CCCCCCCCC/C(C(O)=O)=C([H])\C(C1=O)=C(C(C(OC)=C1OC)=O)C
Formula C21H30O6 M.Wt 378.46
Solubility ≥ 75.4mg/mL in DMSO, ≥ 75.4mg/mL in EtOH Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

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1 mg 5 mg 10 mg
1 mM 2.6423 mL 13.2114 mL 26.4229 mL
5 mM 0.5285 mL 2.6423 mL 5.2846 mL
10 mM 0.2642 mL 1.3211 mL 2.6423 mL
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Average Rating: 5 ★★★★★ (Based on Reviews and 16 reference(s) in Google Scholar.)

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