Columbin - COX 抑制剂 - 生命科学试剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEColumbinCat. No.: HY-N0389CAS No.: 546-97-4分式: CHO分量: 358.39作靶点: COX作通路: Immunology/Inflammation储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 100 mg/mL (279.03 mM)H2O : 40% PEG300 5% Twee

2、n-80 45% salineSolubility: 2.5 mg/mL (6.98 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (6.98 mM); Clear solution1/3 Master of Small Molecules 您边的抑制剂师www.MedChemEBIOLOGICAL ACTIVITY物活性 Columbin具有抗炎活性的萜类螺内酯。体外研究 Treatment with columbin or l-NAME inhibits LPS/IFN-induced

3、 NO production without affecting the viabilityof RAW264.7. Pre-treatment of stimulated cells with columbin does not inhibit the translocation of NF-B tothe nucleus in LPS-stimulated cells. COX-1 and COX-2 inhibitory activities of columbin are 63.76.4% and18.81.5% inhibition at 100M, respectively. Th

4、e interaction of columbin with Tyr385 and Arg120 signifies itshigher activity in COX-2, as Tyr385 is reported to be involved in the abstraction of hydrogen from C-13 ofarachidonate, and Arg120 is critical for high affinity arachidonate binding 1.体内研究 Columbin inhibits oedema formation in mice paw. A

5、t doses of 300 mg/kg and 700 mg/kg, columbin inhibitsinflammation from 0 to 5 h and the results are comparable to that of aspirin as a standard anti-inflammatorydrug. The inhibitory effect of columbin on carrageenan induced paw oedema in mice may be due to thesuppression of the release of mediators

6、responsible for inflammation including prostaglandin 1. Columbin ispoorly bioavailable (2.8% p.o. and 14% i.p.) in rats, but its transport is rapid across the Caco-2 cellmonolayers, suggesting that extensive first-pass metabolism in the liver is the likely reason for its poorbioavailability 2.PROTOC

7、OLAnimal Rats: Male Wistar rats are treated as following: i.v. injection of columbin in EtOH and PEG-300 (1:1) isAdministration 12 administrated through tail vein at dose of 20 mg/kg. Intraperitoneal (i.p.) injection of columbin in EtOH andPEG-300 (1:1) is administrated at dose of 20 mg/kg. An oral

8、gavage of columbin suspended in oralsuspension vehicle is given to rats at dose of 50 mg/kg. Blood samples (50-100 L) are collected by snippingthe tail into heparinized tubes at 0, 5, 15, 30, 45, 60, 120, 240, 360, 480 and 1440 min for i.v. administration,or at 0, 15, 30, 60,120, 180, 240, 360, 480,

9、 1440 min for oral dosing or i.p. injection. The blood samples arestored at 20C until analysis 2.Mice: Male Balb/c mice (n=60) are randomly divided into six groups. Columbin is intra-peritoneallyadministered to mice at the dose of 30, 100, 300 and 700 mg/kg. Aspirin, an anti-inflammatory drug, is us

10、edas a positive control. To induce acute phase inflammation in paw, rats are injected subcutaneously into theright hind paw with a 1% solution of carrageenan dissolved in saline 30 min after vehicle or columbintreatment. The paw volumes are measured up to 5 h after the injection at intervals of 1 h.

11、 Paw volume ismeasured with a plethysmometer immediately prior to the injection of carrageenan and thereafter at aninterval of 1 h for a period of 5 h 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Ibrahim Abdelwahab S, et al. In vitro a

12、nd in vivo anti-inflammatory activities of columbin through the inhibition of cycloxygenase-2 andnitric oxide but not the suppression of NF-B translocation. Eur J Pharmacol. 2012 Mar 5;678(1-3):61-70.2. Yang G, et al. Development and validation of an UPLC-MS/MS method for the quantification of columbin in biological matrices:2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEApplications to absorption, metabolism, and pharmacokinetic studies. J Chromatogr B Analyt Technol Biomed Life Sci. 2015 Oct 1;1002:13-8.McePdfHeigh