Guadecitabine-sodium-SGI-110-sodium-DataSheet-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEGuadecitabine sodiumCat. No.: HY-15229CAS No.: 929904-85-8Synonyms: SGI-110 sodium; S-110 sodium分式: CHNNaOP分量: 579.39作靶點: DNA Methyltransferase作通路: Epigenetics儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 mont

2、h溶解性數(shù)據(jù)體外實驗 DMSO : 50 mg/mL (86.30 mM; Need ultrasonic)H2OMass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 1.7260 mL 8.6298 mL 17.2595 mL5 mM 0.3452 mL 1.7260 mL 3.4519 mL10 mM 0.1726 mL 0.8630 mL 1.7260 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。體內(nèi)實驗請根據(jù)您的實驗動物和給藥式選擇適當(dāng)?shù)娜芙獍?，配制前請先配制澄清的儲備液，再依次添加助溶?

3、為保證實驗結(jié)果的可靠性，體內(nèi)實驗的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使；澄清的儲備液可以根據(jù)儲存條件，適當(dāng)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: 2.5 mg/mL (4.31 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (4.31 mM); Clear solution1/3 Master of Small Mol

4、ecules 您邊的抑制劑師www.MedChemE3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (4.31 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Guadecitabine sodium (SGI-110 sodium; S-110 sodium)由5-Aza-CdR和脫氧鳥苷組成的核苷酸，是有效的DNA甲基化 (DNA methylation inhibitor) 抑制劑。IC50 & Target DNMT1體外研究 After HCT116 colorectal carci

5、noma cells are treated for 6 days, a dose-dependent increase in p16expressionis observed with Guadecitabine sodium (SGI-110 sodium). In addition, T24 and HCT116 cells treated withGuadecitabine sodium or 5-aza-CdR for 3 days show a dose-dependent increase in the level of p16 protein,showing the compe

6、tence of Guadecitabine sodium to inhibit DNA methylation and induce p16 at both mRNAand protein levels as well as 5-aza-CdR. Thus, Guadecitabine sodium is able to inhibit DNA methylation at 5-region and induce the expression of the p16 gene in T24 and HCT116 cells at concentrations comparable to5-az

7、a-CdR, and the induction of p16 expression by both agents correlates with the demethylation at the 5-end region of the gene in both cell lines. Guadecitabine sodium is slightly less toxic than 5-aza-CdR at thedoses tested up to 1 M concentration but displaying similar toxicity at 10 M concentration

8、1.體內(nèi)研究 Guadecitabine sodium (SGI-110 sodium) at 10mg/kg is an effective dose at reducing DNA methylation andretarding tumor growth, and caused roughly the same level of toxicity as 5-Aza-CdR. Guadecitabine sodiumis effective in vivo at reactivating the expression of the p16 gene, which is heavily me

9、thylated in the parentEJ6 cells. Guadecitabine sodium is effective in reducing the level of DNA methylation in vivo at the p16promoter region. Guadecitabine sodium is better tolerated than 5-Aza-CdR in vivo, suggesting that it can bean attractive alternative for potential clinical use 2.PROTOCOLCell

10、 Assay 1 T24 cells are plated at a low density (100 per 60-mm dish) and treated with varying concentrations of 5-aza-CdR and S-110 (0.1, 0.2, 10 M. Colonies are allowed to form for 10 to 14 days, fixed with methanol, andstained with 10% Giemsa. The number of colonies from an untreated control plate

11、is used to calculate theplating efficiency in percent at each concentration. Triplicate dishes are used, and error bars are representedby 1 SD of the mean 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mouse: Athymic nu/nu mice are inoculated

12、subcutaneously in the right hind flank with 107 EJ6 bladderAdministration 2 cancer cells. After tumors reach 0.5 cm in diameter, animals are stratified into three groups with eightanimals per group to begin treatments. Doses and dosing schedules are designed so that each groupreceived molar equivale

13、nts of either S-110 or 5-Aza-CdR. The agents are administered SQ once weekly at adose of 12.2 mg/kg for S-110 and 5.0 mg/kg for 5-Aza-CdR for three weeks. The study includes anappropriate PBS control group. Tumor sizes by caliper and body weight measurements are taken twice2/3 Master of Small Molecu

14、les 您邊的抑制劑師www.MedChemEweekly to monitor tumor growth inhibition and tolerability 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Yoo CB, et al. Delivery of 5-aza-2-deoxycytidine to cells using oligodeoxynucleotides. Cancer Res. 2007 Jul 1;67(13):6400-8.2. Chuang JC, et al. S-110, a 5-Aza-2-deoxycytidine-containing dinucleotide, is an effective DNA methylation inhibitor in vivo and canreduce tumor growth. Mol Cancer Ther. 201