(-)-DHMEQ (Dehydroxymethylepoxyquinomicin) (Synonyms: Dehydroxymethylepoxyquinomicin) |
رقم الكتالوجGC32705
One-Click Copy Product Info
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(-) - DHMEQ (Dehydroxymethylepoxyquinomicin) (Dehydroxymethylepoxyquinomicin) هو مادة NF-κ قوية وانتقائية ولا رجعة فيها ؛ مثبط B الذي يرتبط تساهميًا ببقايا السيستين.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 287194-40-5
Sample solution is provided at 25 µL, 10mM.
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(-)-DHMEQ (Dehydroxymethylepoxyquinomicin) is a selective and irreversible NF-κB inhibitor. (-)-DHMEQ directly and covalently binds to specific cysteine residues of Rel family proteins (p65, cRel, RelB, p50). (-)-DHMEQ inhibits NF-κB DNA-binding activity and nuclear translocation. (-)-DHMEQ blocks canonical and non-canonical NF-κB signaling pathways. (-)-DHMEQ reduces the expression of inflammatory cytokines, adhesion molecules, and anti-apoptotic proteins. (-)-DHMEQ can be used in studies related to malignant tumors such as prostate cancer, bladder cancer, adult T-cell leukemia, and pancreatic cancer metastasis, as well as inflammatory diseases including rheumatoid arthritis, sepsis, atopic dermatitis, asthma, and transplant rejection[1-4].
In vitro, pretreatment of INS-1 cells with 1-5µg/mL (-)-DHMEQ for 2 hours followed by co-treatment with 100ng/mL TNF-α for 24 hours inhibited TNF-α-induced NF-κB activation, improved TNF-α-suppressed glucose-stimulated insulin secretion, and ameliorated TNF-α-reduced cell viability[5]. Treatment of MT-2 cells with 1-5µg/mL (-)-DHMEQ for 1-4 hours reduced nuclear p65 protein levels and inhibited NF-κB DNA-binding activity in nuclear extracts[6]. Treatment of A2780 cells with 1.56-100µg/mL (-)-DHMEQ for 24, 48, or 72 hours time-dependently reduced cell viability, decreased colony formation number, and increased the proportion of necrotic and late apoptotic cells[7].
In vivo, C57BL/6 mice treated with 3% dextran sulfate sodium (DSS) received intraperitoneal injections of 20mg/kg (-)-DHMEQ twice daily for 10 consecutive days. (-)-DHMEQ improved disease activity index scores, alleviated colon edema, and reduced histological damage scores[8]. Pristane-treated BALB/c mice received intraperitoneal injections of 12mg/kg (-)-DHMEQ three times per week for 16 consecutive weeks. (-)-DHMEQ reduced serum levels of anti-nucleosome, anti-dsDNA, and anti-histone IgG autoantibodies, and alleviated glomerular damage and renal pathological changes[9]. NOD/SCIDβ2mnull mice bearing TL-Om1 cell subcutaneous xenografts behind the ear received intraperitoneal injections of 12mg/kg (-)-DHMEQ three times per week for 5 consecutive weeks. (-)-DHMEQ inhibited subcutaneous xenograft tumor growth and induced TUNEL-positive apoptotic cells in tumor tissues[10].
References:
[1] Umezawa K, Breborowicz A, Gantsev S. Anticancer Activity of Novel NF-kappa B Inhibitor DHMEQ by Intraperitoneal Administration. Oncol Res. 2020 Dec 10;28(5):541-550.
[2] Ma J, Zhang Y, Sugai T, et al. Inhibition of Cellular and Animal Inflammatory Disease Models by NF-κB Inhibitor DHMEQ. Cells. 2021 Sep 1;10(9):2271.
[3] Lin Y, Ukaji T, Koide N, et al. Inhibition of Late and Early Phases of Cancer Metastasis by the NF-κB Inhibitor DHMEQ Derived from Microbial Bioactive Metabolite Epoxyquinomicin: A Review. Int J Mol Sci. 2018 Mar 3;19(3):729.
[4] Umezawa K. Possible role of peritoneal NF-κB in peripheral inflammation and cancer: lessons from the inhibitor DHMEQ. Biomed Pharmacother. 2011 Jul;65(4):252-9.
[5] Saisho Y, Hirose H, Horimai C, et al. Effects of DHMEQ, a Novel Nuclear Factor-κB Inhibitor, on Beta Cell Dysfunction in INS-1 Cells. Endocr J. 2008;55(2):433-438.
[6] Horie K, Ma J, Umezawa K. Inhibition of Canonical NF-κB Nuclear Localization by (-)-DHMEQ via Impairment of DNA Binding. Oncol Res. 2015;22(3):105-115.
[7] Michalak M, Lach MS, Borska S, et al. DHMEQ enhances the cytotoxic effect of cisplatin and carboplatin in ovarian cancer cell lines. Am J Cancer Res. 2021;11(12):6024-6041.
[8] Funakoshi T, Yamashita K, Ichikawa N, et al. A novel NF-κB inhibitor, dehydroxymethylepoxyquinomicin, ameliorates inflammatory colonic injury in mice. J Crohns Colitis. 2012;6(2):215-225.
[9] Qu H, Bian W, Xu Y. A novel NF-kB inhibitor, DHMEQ, ameliorates pristane-induced lupus in mice. Exp Ther Med. 2014 Jul;8(1):100-104.
[10] Ohsugi T, Kumasaka T, Okada S, et al. Dehydroxymethylepoxyquinomicin (DHMEQ) therapy reduces tumor formation in mice inoculated with Tax-deficient adult T-cell leukemia-derived cell lines. Cancer Lett. 2007 Oct 8;257(2):206-215.
| Cell experiment [1]: | |
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Cell lines |
INS-1 cells (rat insulinoma beta cell line) |
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Preparation Method |
INS-1 cells were cultured in RPMI-1640 medium containing 11.1mM glucose, 10mM HEPES, 10% heat-inactivated fetal calf serum, 1mM sodium pyruvate, 2mM L-glutamine, 50μM β-mercaptoethanol, and 60μg/mL kanamycin at 37°C, 5% CO2. Cells were pre-treated with (-)-DHMEQ at 1-5μg/ml for 2h, then co-incubated with 100ng/ml TNF-α for 24h. After treatment, glucose-stimulated insulin secretion by 60min KRB-HEPES challenge and EIA, cell viability by MTT assay, and mRNA levels of insulin, GCK, GLUT2, PDX-1 by quantitative real-time RT-PCR. |
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Reaction Conditions |
1-5μg/mL; 2h pre-treatment |
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Applications |
(-)-DHMEQ suppressed TNF-α-induced NF-κB activation in INS-1 cells. (-)-DHMEQ partially ameliorated TNF-α-induced inhibition of glucose-stimulated insulin secretion. (-)-DHMEQ partially restored TNF-α-suppressed mRNA levels of insulin, GCK and GLUT2. (-)-DHMEQ partially ameliorated TNF-α-induced reduction in cell viability. |
| Animal experiment [2]: | |
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Animal models |
8-week-old female BALB/c mice with pristane-induced lupus (0.5mL pristane i.p. at week 0) |
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Preparation Method |
When mice reached 16 weeks of age (8 weeks after pristane injection), intraperitoneal injections of 12mg/kg (-)-DHMEQ or vehicle were administered three times per week until mice were 32 weeks old (16 weeks of treatment). Serum was collected from tail vein at weeks 8, 16, 32 for anti-nucleosome/anti-dsDNA/anti-histone IgG ELISA; at week 32 mice were CO2 euthanized, kidneys removed for 24h urine protein (metabolic cage), H&E histology, and Western blot of p-p38 MAPK, p-JNK, NF-κB p65. |
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Dosage form |
12mg/kg; i.p.; three times per week for 16 weeks |
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Applications |
(-)-DHMEQ lowered serum anti-dsDNA IgG at week 32. (-)-DHMEQ lowered serum anti-nucleosome IgG at week 32. (-)-DHMEQ lowered serum anti-histone IgG at week 32. (-)-DHMEQ lowered serum TNF-α, IL-1β, IL-6 and IL-17 levels at week 32. (-)-DHMEQ reduced 24h urinary protein excretion at week 32. (-)-DHMEQ reduced glomerular damage and renal histological lesions. (-)-DHMEQ downregulated renal phosphorylated-p38 MAPK, phosphorylated-JNK and NF-κB p65 protein levels. |
References: [1] Saisho Y, Hirose H, Horimai C, et al. Effects of DHMEQ, a Novel Nuclear Factor-κB Inhibitor, on Beta Cell Dysfunction in INS-1 Cells. Endocr J. 2008;55(2):433-438. [2] Qu H, Bian W, Xu Y. A novel NF-kB inhibitor, DHMEQ, ameliorates pristane-induced lupus in mice. Exp Ther Med. 2014 Jul;8(1):100-104. | |
| Cas No. | 287194-40-5 | SDF | |
| المرادفات | Dehydroxymethylepoxyquinomicin | ||
| Canonical SMILES | O=C1[C@@H](O2)[C@@H]2[C@@H](O)C(NC(C3=C(O)C=CC=C3)=O)=C1 | ||
| Formula | C13H11NO5 | M.Wt | 261.23 |
| الذوبان | DMSO : ≥ 32 mg/mL (122.50 mM) | Storage | Store at -20°C |
| 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 | 3.828 mL | 19.1402 mL | 38.2804 mL |
| 5 mM | 765.6 μL | 3.828 mL | 7.6561 mL |
| 10 mM | 382.8 μL | 1.914 mL | 3.828 mL |
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- Purity: >98.50% Appearance: A solid
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Average Rating: 5 (Based on Reviews and 33 reference(s) in Google Scholar.)