E3330 (Synonyms: APX 3330) |
| Katalog-Nr.GC10620 |
E3330 ist ein niedermolekularer Inhibitor der apurinischen/apyrimidinischen Endonuklease/Redox-Effektor-Funktion (APE1/Ref-1) des Redox-Domänensystems (IC50, 50 µmol/L).
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 136164-66-4
Sample solution is provided at 25 µL, 10mM.
E3330 ist ein niedermolekularer Inhibitor der apurinischen/apyrimidinischen Endonuklease/Redox-Effektor-Funktion (APE1/Ref-1) des Redox-Domänensystems (IC50, 50 µmol/L) [1,2].
E3330 (10-30 µM, 72h) hemmt nicht nur das Wachstum, sondern auch die Migrationsfähigkeiten von Pankreaskrebszellen in vitro [1]. Die gemeinsame Inkubation von E3330 (30 µM, 3 h) und Cisplatin (5-20 µM, 72 h) verringerte die Zellviabilität in der humanen NSCLC-Zelllinie H1975 im Vergleich zu Cisplatin allein signifikant [3]. Die Behandlung mit E3330 verhinderte die funktionelle Aktivierung von NF-κB durch die Veränderung des subzellulären Transports von APE1 und reduzierte die durch TNF-α induzierte Expression von IL-6 und IL-8 [4]. E3330 unterdrückte deutlich die Sekretion von entzündlichen Zytokinen einschließlich Tumornekrosefaktor-α (TNF-α), Interleukin (IL-6) und IL-12 sowie entzündliche Mediatoren wie Stickstoffmonoxid (NO) und Prostaglandin E2 (PGE2) aus den LPS-stimulierten RAW264.7-Zellen [5].
Die Behandlung mit E3330 (10-100 mg/kg, oral) 1 Stunde nach der Galaktosamin-Herausforderung verringerte die Leberschädigung. E3330 war wirksam, wenn es p.o. 6 oder 12 Stunden nach der Galaktosamin-Herausforderung im Galaktosamin-induzierten Hepatitis-Modell bei F344-Ratten verabreicht wurde [6]. Die Injektion von TNF in Kombination mit Galaktosamin führte zu schweren Leberschäden. Eine orale Vorbehandlung mit 100 und 300 mg/kg E3330 30 Minuten vor der Injektion von Galaktosamin/TNF verringerte signifikant den Anstieg der Plasma-L-Alanin-Aminotransferase- und L-Aspartat-Aminotransferase-Aktivitäten [7]. Die geschätzte Halbwertszeit (t1/2) von E3330 betrug 3,7 Stunden bei Mäusen [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.
| 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 [1]: | |
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: | |
| Cas No. | 136164-66-4 | SDF | |
| Überlieferungen | 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 |
| Löslichkeit | ≥ 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. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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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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Quality Control & SDS
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- Purity: >98.00%
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Average Rating: 5 (Based on Reviews and 16 reference(s) in Google Scholar.)
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