E3330 (APX-3330)

Alias:
Cat No.:V1432 Purity: ≥98%
E3330(E-3330; E 3330; APX-3330; APX 3330;APX3330)is a potent,orally bioactive and selective APE1 (Ref-1, AP endonuclease 1) inhibitor with potential antitumor activity.
E3330 (APX-3330) Chemical Structure CAS No.: 136164-66-4
Product category: DNA(RNA) Synthesis
This product is for research use only, not for human use. We do not sell to patients.
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Purity & Quality Control Documentation

Purity: ≥98%

Product Description

E3330 (E-3330; E 3330; APX-3330; APX 3330; APX3330) is a potent, orally bioactive and selective APE1 (Ref-1, AP endonuclease 1) inhibitor with potential antitumor activity.

Biological Activity I Assay Protocols (From Reference)
Targets
NF-κB; APE1(Ref-1)
ln Vitro

In vitro activity: E3330 inhibits Ape1 redox activity, which has an impact on hemangioblast development in vitro.[1] The human pancreatic cancer cell lines PANC1, XPA1, MIAPACA, BxPC3, and PK9 are all inhibited in their growth by E3330. Additionally, E3330 encourages PANC1 cells to exit the cell cycle, inhibits HIF-1α's DNA-binding activity, and prevents pancreatic cancer cells from migrating.[2] In JHH6 cells, E3330 blocks FAs accumulation and TNF-α-induced IL-6 and IL-8 expression by blocking redox-mediated activation of NF-κB. It also prevents the functional activation of NF-κB by changing APE1 subcellular trafficking.[3]

ln Vivo
E3330 (300 mg/kg, p.o.) attenuates the elevation of plasma tumor necrosis factor activity and shields mice against liver damage in endotoxin-mediated hepatitis.[4] E3330 (100 mg/kg, p.o.) also shields rats against severe liver damage caused by galactosamine and endotoxin in a rat model.[5]
Cell Assay
PANC1 cells are treated with 5 to 30 μM E3330 after being inserted into one well of a 12-well plate. Following cultures for 24, 48, and 72 hours, the cells are rinsed with PBS, stained with trypan blue, and their viability is assessed by counting the number of living cells.
Animal Protocol
Suspended in 0.5% methylcellulose solution; 300 mg/kg; p.o.
Mice with endotoxin-mediated hepatitis
References

[1]. Blood . 2007 Mar 1;109(5):1917-22.

[2]. Mol Cancer Ther . 2008 Jul;7(7):2012-21.

[3]. PLoS One . 2013 Aug 15;8(8):e70909.

[4]. J Pharmacol Exp Ther . 1992 Jul;262(1):145-50.

[5]. J Pharmacol Exp Ther . 1993 Jan;264(1):496-500.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C21H30O6
Molecular Weight
378.46
Exact Mass
378.2
Elemental Analysis
C, 66.65; H, 7.99; O, 25.36
CAS #
136164-66-4
Related CAS #
136164-66-4
Appearance
Solid powder
SMILES
CCCCCCCCC/C(=C\C1=C(C(=O)C(=C(C1=O)OC)OC)C)/C(=O)O
InChi Key
AALSSIXXBDPENJ-FYWRMAATSA-N
InChi Code
InChI=1S/C21H30O6/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)/b15-13+
Chemical Name
(2E)-2-[(4,5-dimethoxy-2-methyl-3,6-dioxocyclohexa-1,4-dien-1-yl)methylidene]undecanoic acid
Synonyms

E3330; E-3330; E 3330

HS Tariff Code
2934.99.9001
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO: 75~120 mg/mL (198.2~317.1 mM)
Water: ~75 mg/mL (~198.2 mM)
Ethanol: <1 mg/mL
Solubility (In Vivo)
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.50 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

Solubility in Formulation 2: ≥ 2.08 mg/mL (5.50 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (5.50 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.


 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 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

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

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What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
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What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
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Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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Calculation results

Working concentration mg/mL;

Method for preparing DMSO stock solution mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.

(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
             (2) Be sure to add the solvent(s) in order.

Clinical Trial Information
NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT03375086 Completed Drug: APX3330 Cancer Apexian Pharmaceuticals, Inc. January 30, 2018 Phase 1
Biological Data
  • NF-κB transcription factor regulates IL-8 promoter activity in JHH6 cells and E3330 treatment inhibits TNF-α-induced promoter activation. PLoS One . 2013 Aug 15;8(8):e70909.
  • E3330 treatment specifically inhibits TNF-α- and FAs-induced IL-8 endogenous gene expression. PLoS One . 2013 Aug 15;8(8):e70909.
  • Hypoxia enhances E3330-mediated growth inhibition in pancreatic cancer cells. Mol Cancer Ther . 2008 Jul;7(7):2012-21
  • E3330 enhances ROS production in PANC1 cells. Mol Cancer Ther . 2008 Jul;7(7):2012-21
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