SecinH3-DataSheet-生命科學試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemESecinH3Cat. No.: HY-100559CAS No.: 853625-60-2分式: CHNOS分量: 460.51作靶點: Others作通路: Others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 : 100 mg/mL (217.15 mM; Need ultrasonic and warming)Mass

2、 Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 2.1715 mL 10.8575 mL 21.7151 mL5 mM 0.4343 mL 2.1715 mL 4.3430 mL10 mM 0.2172 mL 1.0858 mL 2.1715 mL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 SecinH3是cytohesins 的拮抗劑，對于 hCyh1， hCyh2，mCyh3，hCyh3，drosophila steppke 和 yGea2-S7的 IC5

3、0 值分別為 5.4 M，2.4 M，5.4 M，5.6 M，5.6 M 和 65 M。IC50 & Target IC50: 5.4 M (hCyh1)，2.4 M (hCyh2)，5.4 M (mCyh3)，5.6 M (hCyh3)，5.6 M (drosophilasteppke), 65 M (yGea2-S7) 1體外研究SecinH3 is a Sec7-specific guanine nucleotide exchange factor (GEF) inhibitor with preference for the small1/2 Master of Small Molec

4、ules 您邊的抑制劑師www.MedChemEGEFs of the cytohesin family. SecinH3 almost completely blocks the insulin-dependent transcriptionalrepression of IGFBP1 with an IC50 of 2.2 M. Insulin-stimulated translocation of ARF6 to the plasmamembrane is also inhibited by SecinH3. It is found that SecinH3 inhibits the i

5、nsulin-dependentphosphorylation of Akt and FoxO1A in a concentration-dependent manner. Insulin-induced exclusion ofFoxO1A from the nucleus is completely prevented by SecinH3. The binding of IRS1 to the insulin receptor isalso inhibited by SecinH3 1.體內(nèi)研究 Compare to mice fed the same chow without Seci

6、nH3, the expression levels of the insulin-repressedgluconeogenic genes are elevated, whereas the insulin-induced glycolytic genes are reduced in SecinH3-treated mice. Insulin-stimulated Akt phosphorylation is also inhibited in SecinH3-treated mice. Theexpression of the genes for two key enzymes of m

7、itochondrial -oxidation, carnitine palmitoyltransferase 1a(Cpt1a) and hydroxyacyl-CoA dehydrogenase (Hadha), both of which are repressed by insulin, is increasedin the SecinH3-treated mice. It is found significantly increased levels of serum insulin with slightly elevatedglucose concentrations in Se

8、cinH3-treated mice. Accordingly, 3-hydoxybutyrate is increased in the serum ofSecinH3-treated mice 1.PROTOCOLCell Assay 1 105 HepG2 cells are seeded in 12 well plates and cultured for 24 h in EMEM containing 10 % FCS. Cells arethen serum starved in EMEM for 24 h and stimulated for 12 h with 10 nM in

9、sulin in the presence of SecinH3,the negative control D5 or vehicle (0.2% final concentration of DMSO). Total mRNA is prepared using Kit andcDNA for qPCR is generated from 1 g RNA. qPCR is performed and data are normalized to 2-microglobulin expression 1.MCE has not independently confirmed the accur

10、acy of these methods. They are for reference only.Animal C57/Bl6N mice are kept on a 12 h light/dark cycle in a pathogen-free animal facility and fed ad libitum withAdministration 1 standard mice diet. After feeding with standard diet or with the same diet containing 0.9 mol/g SecinH3 for 3days, mic

11、e are intraperitoneally injected with 100 L saline containing or not 40 g recombinant humaninsulin. After 10 min the mice are anaesthetized and the liver is removed and lysed in lysis buffer. Normalizedamounts of protein are either separated by SDSand transferred onto nitrocellulose, orimmunoprecipi

12、tated using agarose-conjugated antibodies against IR or IRS1 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Hafner M, et al. Inhibition of cytohesins by SecinH3 leads to hepatic insulin resistance. Nature. 2006 Dec 14;444(7121):941-4.McePdfHeightCaution: P