環(huán)氧酶素作用機(jī)制 - Medchemexpress - MCE中國(guó)

1、Product Data SheetEpoxomicinCat. No.: HY-13821CAS No.: 134381-21-8分式: CHNO分量: 554.72作靶點(diǎn): Proteasome; Apoptosis作通路: Metabolic Enzyme/Protease; Apoptosis儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 100 mg/mL (180.27 mM; Need ultrasonic)SolventMass1 mg 5 mg 10

2、mgConcentration制備儲(chǔ)備液1 mM 1.8027 mL 9.0136 mL 18.0271 mL5 mM 0.3605 mL 1.8027 mL 3.6054 mL10 mM 0.1803 mL 0.9014 mL 1.8027 mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲(chǔ)備液；旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?6 個(gè)內(nèi)使，-20C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?1 個(gè)內(nèi)使。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍浮Ｒ韵氯芙獍付颊?qǐng)先按照 In Vitro

3、 式配制澄清的儲(chǔ)備液，再依次添加助溶劑：為保證實(shí)驗(yàn)結(jié)果的可靠性，澄 的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使； 以下溶劑前顯的百分 指該溶劑在您配制終溶液中的體積占；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的式助溶1. 請(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (4.51 mM); Clear solution此案可獲得 2.5 mg/mL (4.51 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 25.0 mg/

4、mL 的澄 DMSO 儲(chǔ)備液加到 400 L PEG300 中，混合均勻；向上述體系中加50 L Tween-80，混合均勻；然后繼續(xù)加 450 L 理鹽定容 1 mL。2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (4.51 mM); Clear solution此案可獲得 2.5 mg/mL (4.51 mM，飽和度未知) 的澄清溶液。Page 1 of 2 www.MedChemE以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄均勻。DMSO 儲(chǔ)備液加到 900 L 20%

5、的 SBE-CD 理鹽溶液中，混合3. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (4.51 mM); Clear solution此案可獲得 2.5 mg/mL (4.51 mM，飽和度未知) 的澄 溶液，此案不適于實(shí)驗(yàn)周 期在半個(gè)以上的實(shí)驗(yàn)。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲(chǔ)備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性 Epoxomicin (BU-4061T) 種含環(huán)氧酮的天然產(chǎn)物， 種有效的，選擇性的和不可逆的蛋酶體 (proteasom

6、e) 抑 制劑。Epoxomicin 與蛋酶體的LMP7，X，MECL1 和 Z 催化亞 共價(jià)結(jié)合，并有效地主 抑制類胰凝乳蛋酶的活性 。Epoxomicin 可以穿越腦屏障，并具有很強(qiáng)的抗腫瘤和抗炎活性。IC & Target Proteasome1體外研究 Epoxomicin shows quite potent cytotoxicities against all of the cells tested. Epoxomicin inhibits the cells growth ofB16-F10, HCT116, Moser, P388 and K562 cells of IC50

7、values of 0.002 g/mL, 0.005 g/mL, 0.044 g/mL, 0.002 g/mLand 0.037 g/mL1.Epoxomicin has antiproliferative activity with an IC50 of 4 nM in EL4 lymphoma cells2.體內(nèi)研究 Epoxomicin (0.063-1 mg/kg; intraperitoneal injection; once daily; for 9 days; male BDFX mice) treatment showssignificant antitumor effect

8、 with the minimumeffective dose of 0.13mg/kg/day1.Epoxomicin also effectively inhibits NF-B activation in vitro and potently blocks in vivo inflammation in the murine ear edema assay3.Epoxomicin is injected into adult rats over a period of 2 weeks. After a latency of 1 to 2 weeks, animals developedp

9、rogressive Parkinsonism with bradykinesia, rigidity, tremor, and an abnormal posture. Postmortem analyses showsstriatal dopamine depletion and dopaminergic cell death with apoptosis in the substantia nigra pars compacta4.Animal Model: Male BDFX mice with B16 melanoma1Dosage: 0.063 mg/kg, 0.13 mg/kg,

10、 0.25 mg/kg, 0.5 mg/kg, 1 mg/kgAdministration: Intraperitoneal injection; once daily; for 9 daysResult: Exhibited strong therapeutic activity against B16 melanoma.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Mol Plant Pathol. 2018 Dec;19(12):2623-2634.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1.

11、Kim KB, et al. Proteasome inhibition by the natural products epoxomicin and dihydroeponemycin: insights into specificity and potency. Bioorg MedChem Lett. 1999 Dec 6;9(23):3335-40.Page 2 of 3 www.MedChemE2. Hanada M, et al. Epoxomicin, a new antitumor agent of microbial origin. J Antibiot (Tokyo). 1

12、992 Nov;45(11):1746-52.3. Garrett IR, et al. Selective inhibitors of the osteoblast proteasome stimulate bone formation in vivo and in vitro. J Clin Invest. 2003 Jun;111(11):1771-82.4. McNaught KS, et al. Systemic exposure to proteasome inhibitors causes a progressive model of Parkinsons disease. Ann Neurol. 2004 Jul;56(1):149-62.5. Meng L, et al. Epoxomicin, a potent and selective proteasome inhibitor, exhibits in vivo antiinflammatory activity. Proc Natl Acad Sci U S A. 1999 Aug31;96(18):10403-8.McePdfHeightCaution: Product has