1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEChenodeoxycholic AcidCat. No.: HY-76847CAS No.: 474-25-9Synonyms: CDCA分式: CHO分量: 392.57作靶點: FXR; Endogenous Metabolite作通路: Metabolic Enzyme/Protease儲存式: 4C, protect from light* In solvent : -80C, 6 months; -20C, 1 month (protect

2、 fromlight)溶解性數(shù)據(jù)體外實驗 DMSO : 50 mg/mL (127.37 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 2.5473 mL 12.7366 mL 25.4732 mL5 mM 0.5095 mL 2.5473 mL 5.0946 mL10 mM 0.2547 mL 1.2737 mL 2.5473 mL請根據(jù)產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。體內實驗請根據(jù)您的實驗動物和給藥式

3、選擇適當?shù)娜芙獍?，配制前請先配制澄清的儲備液，再依次添加助溶?為保證實驗結果的可靠性，體內實驗的作液，建議您現(xiàn)現(xiàn)配，當天使；澄清的儲備液可以根據(jù)儲存條件，適當保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 5 mg/mL (12.74 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 5 mg/mL (12.74 mM); Clear s

4、olution3. 請依序添加每種溶劑： 10% DMSO 90% corn oil1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemESolubility: 5 mg/mL (12.74 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Chenodeoxycholic Acid種疏初級膽汁酸，能夠活化核受體 FXR，該受體與膽固醇代謝有關。IC50 & Target Human Endogenous Metabolite體外研究 Chenodeoxycholic acid (CDCA) and Deoxycho

5、lic acid (DCA) both inhibit 11 beta HSD2 with IC50 values of22 mM and 38 mM, respectively and causes cortisol-dependent nuclear translocation and increasestranscriptionalactivity of mineralocorticoid receptor (MR) 1. Chenodeoxycholic acid is able to stimulateIshikawa cell growth by inducing a signif

6、icant increase in Cyclin D1 protein and mRNA expression throughthe activation of the membrane G protein-coupled receptor (TGR5)-dependent pathway 2.Chenodeoxycholic acid (CDCA) induces LDL receptor mRNA levels approximately 4 fold and mRNA levelsfor HMG-CoA reductase and HMG-CoA synthase two fold in

7、 a cultured human hepatoblastoma cell line, HepG2 3. Chenodeoxycholic acid-induced Isc is inhibited (67%) by Bumetanide, BaCl2, and the cystic fibrosistransmembrane conductance regulator (CFTR) inhibitor CFTRinh-172. Chenodeoxycholic acid-stimulated Iscis decreased 43% by the adenylate cyclase inhib

8、itor MDL12330A and Chenodeoxycholic acid increasesintracellular cAMP concentration 4. Chenodeoxycholic acid treatment activates C/EBP, as shown byincreases in its phosphorylation, nuclear accumulation, and expression in HepG2 cells. Chenodeoxycholicacid enhances luciferase gene transcription from th

9、e construct containing -1.65-kb GSTA2 promoter, whichcontains C/EBP response element (pGL-1651). Chenodeoxycholic acid treatment activates AMP-activatedprotein kinase (AMPK), which leads to extracellular signal-regulated kinase 1/2 (ERK1/2) activation, asevidenced by the results of experiments using

10、 a dominant-negative mutant of AMPK and chemical inhibitor5.PROTOCOLKinase Assay 1 Briefly, transfected HEK-293 cells, incubated in charcoal-treated Dulbeccos modified Eagles medium for 24h, are washed once with Hanks solution and resuspended in a buffer containing 100 mM NaCl, 1 mM MgCl2,1 mM EDTA,

11、 1 mM EGTA, 250 mMsucrose, 20 mM Tris-HCl, pH 7.4. Cells are lysed by freezing in liquidnitrogen. Dehydrogenase activity is measured in a final volume of 20 L containing the appropriateconcentration of bile acid, 30 nCi of 3Hcortisol, and unlabeled cortisol to a final concentrations of 50 nM.The rea

12、ction is started by mixing cell lysate with the reaction mixture. Alternatively, endoplasmic reticulummicrosomes are prepared from transfected HEK-293 cells and incubated with reaction mixture containingvarious concentrations of cortisol and CDCA. Incubation proceeded for 20 min, and the conversion

13、of cortisolto cortisone is determined by thin layer chromatography (TLC). Because of the inaccuracy of the TLC methodat low conversion rates and the end-product inhibition of 11HSD2 at conversion rates higher than 60-70%,only conversion rates between 10 and 60% are considered for calculation. The in

14、hibitory constant IC50 isevaluated using the curve-fitting program. Results are expressed as meansS.E. and consist of at least fourindependent measurements.MCE has not independently confirmed the accuracy of these methods. They are for reference only.2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE

15、Cell Assay 1 The cell viability is analyzed by incubating transfected HEK-293 cells and CHO cells for 1 h with thecorresponding concentration of bile acid and staining with trypan blue. The toxicity of bile acids is analyzedusing the tetrazolium salt MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltet

16、razolium bromide) according to thecell proliferation kit I. No significant differences between control and bile acid-treated cells are obtained inboth tests.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產品發(fā)表的科研獻 Cell Res. 2019 Mar;29(3):193-205.See

17、 more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Stauffer AT, et al. Chenodeoxycholic acid and deoxycholic acid inhibit 11 beta-hydroxysteroid dehydrogenase type 2 and cause cortisol-induced transcriptional activation of the mineralocorticoid receptor. J Biol Chem. 2002 Jul 19;277(

18、29):26286-922. Casaburi I, et al. Chenodeoxycholic acid through a TGR5-dependent CREB signaling activation enhances cyclin D1 expression andpromotes human endometrial cancer cell proliferation. Cell Cycle. 2012 Jul 15;11(14):2699-7103. Kawabe Y, et al. The molecular mechanism of the induction of the low density lipoprotein receptor by chenodeoxycholic acid in culturedhuman cells. Biochem Biophys Res Commun. 1995 Mar 8;208(1):405-11.4. Ao M, et al. Chenodeoxycholic acid stimulates Cl(-) secretion via cAMP si