1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEOpaganibCat. No.: HY-16015CAS No.: 915385-81-8Synonyms: ABC294640分式: CHClNO分量: 380.91作靶點: SPHK作通路: Immunology/Inflammation儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 3.7 mg/mL (9.71 mM)

2、* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 2.6253 mL 13.1265 mL 26.2529 mL5 mM 0.5251 mL 2.6253 mL 5.2506 mL10 mM - - -請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 Opaganib (ABC294640)種選擇性的競爭性的鞘氨醇激酶 2 (SK2) 抑制劑，Ki 為 9.8 M。IC50 & T

3、arget Ki: 9.8 M (SK2) 1體外研究Using recombinant human SK1 and SK2, Opaganib demonstrates dose-dependent inhibition of SK2 with an1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEIC50 of approximately 60 M without affecting the activity of SK1 at concentrations up to at least 100 M. Incontrast, N,N-dime

4、thylsphingosine (DMS) inhibits both SK1 and SK2 with IC50 values of approximately 60and 20 M, respectively. Kinetic analyses of varying concentrations of Opaganib (ABC294640) in thepresence of 2.5 to 25 M sphingosine indicated a Ki of 9.81.4 M for the inhibition of SK2. Opaganib(ABC294640) decreases

5、 3HS1P formation in a dose-dependent fashion with an IC50 value of 26 M 1.IC50 values for Opaganib (ABC294640) are approximately 50 and 60 M for A-498 and Bxpc-3 cells,respectively; whereas the IC50 values for Opaganib (ABC294640) are approximately 20 and 40 M for thesecells 2.體內(nèi)研究 Opaganib induces

6、a transient minor decrease in the hematocrit of rats. Hematology studies indicatedecreases in red blood cell number and hematocrit of approximately 20% in animals given either 100 or 250mg/kg/day; and a slight increase in neutrophils and decrease in basophils in the treated rats 1. Mice aregavaged w

7、ith Opaganib (50 mg/kg), a selective inhibitor of sphingosine kinase-2 (SK2), 1 h before surgeryand subjected to 1 h-warm ischemia to 70% of the liver followed by reperfusion. Opaganib-treatment largelyprevented the increase of sphingosine-1-phosphate (S1P) after ischemia-reperfusion (IR) in vivo 2.

8、PROTOCOLCell Assay 1 To determine the effects of the test compounds (e.g., Opaganib (ABC294640) on proliferation, cells areplated into 96-well microtiter plates and allowed to attach for 24 h. Varying concentrations of Opaganib areadded to individual wells and the cells are incubated for an addition

9、al 72 h. At the end of this period, thenumber of viable cells is determined by use of the sulforhodamine-binding assay. The percentage of cellskilled is calculated as the percentage decrease in sulforhodamine-binding compare with control cultures.Regression analyses of inhibition curves are performe

10、d by use of GraphPad Prism 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Rats 1Administration 13 Sprague-Dawley male rats (7-8 weeks old) are orally dosed with 0, 100, or 250 mg of ABC294640HCl/kg in0.375% Polysorbate-80 in PBS daily for 7 da

11、ys. The animals are observed daily for viability, signs of grosstoxicity, and behavioral changes, and a battery of detailed observations are performed on study days 1 and7. Blood is sampled from all animals on day 8 of the study for hematology, clinical biochemistry, and serologyassessments, and the

12、 animals are sacrificed. Gross necropsies are performed on all study rats, and selectedorgans and tissues are evaluated in the control and high-dose level groups.Mice 3Male C57BL/6 (8-9 weeks) mice are gavaged with 50 mg/kg of Opaganib (ABC294640), or an equivalentvolume of vehicle (0.375% Tween 80

13、in phosphate buffered saline, pH 7.1) 1 h before surgery. Under etheranesthesia, ischemia to 70% of the total liver is induced for 1 h. After opening the vascular clamp, the non-ischemic liver lobes are removed, and mice are observed 7 days for survival. Sham operation includedequivalent anesthesia

14、and laparotomy without ischemia.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn)2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE FASEB J. 2019 Mar;33(3):3636-3646. Biochim Biophys Acta Mol Basis Dis. 2018 Nov;1864(11):3824-3836. Arch Med Res

15、. 2018 Jul;49(5):335-341. Oncotarget. 2016 Mar 29;7(13):16663-75.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. French KJ, et al. Pharmacology and antitumor activity of ABC294640, a selective inhibitor of sphingosine kinase-2. J Pharmacol ExpTher. 2010 Apr;333(1):129-39.2. Bel

16、janski V, et al. Combined anticancer effects of sphingosine kinase inhibitors and sorafenib. Invest New Drugs. 2011 Dec;29(6):1132-42.3. Shi Y, et al. Sphingosine kinase-2 inhibition improves mitochondrial function and survival after hepatic ischemia-reperfusion. J Hepatol.2012 Jan;56(1):137-45.4. Liu Q, et al. Inhibition of sphingosine kinase-2 suppresses inflammation and attenuates graft injury after liver trans