地西他濱作用機制 - Medchemexpress - MCE中國

1、Product Data SheetDecitabineCat. No.: HY-A0004CAS No.: 2353-33-5分式: CHNO分量: 228.21作靶點: DNA Methyltransferase; Apoptosis; Nucleoside Antimetabolite/Analog作通路: Epigenetics; Apoptosis; Cell Cycle/DNA Damage儲存式: 4C, protect from light* In solvent : -80C, 6 months; -20C, 1 month (protect from light)溶解性數據

2、體外實驗 DMSO : 50 mg/mL (219.10 mM)* means soluble, but saturation unknown.SolventMass1 mg 5 mg 10 mgConcentration制備儲備液1 mM 4.3819 mL 21.9096 mL 43.8193 mL5 mM 0.8764 mL 4.3819 mL 8.7639 mL10 mM 0.4382 mL 2.1910 mL 4.3819 mL請根據產品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；旦配成溶液，請分裝保存，避免反復凍融造成的產品失效。儲備液的保存式和期限：-80C, 6 months

3、; -20C, 1 month (protect from light)。-80C 儲存時，請在 6 個內使，-20C 儲存時，請在 1 個內使。體內實驗請根據您的實驗動物和給藥式選擇適當的溶解案。以下溶解案都請先按照 In Vitro 式配制澄清的儲備液，再依次添加助溶劑：為保證實驗結果的可靠性，澄 的儲備液可以根據儲存條件，適當保存；體內實驗的作液，建議您現現配，當天使； 以下溶劑前顯的百分 指該溶劑在您配制終溶液中的體積占；如在配制過程中出現沉淀、析出現象，可以通過加熱和/或超聲的式助溶1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% s

4、alineSolubility: 2.5 mg/mL (10.95 mM); Clear solution此案可獲得 2.5 mg/mL (10.95 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲備液加到 400 L PEG300 中，混合均勻；向上述體系中加50 L Tween-80，混合均勻；然后繼續(xù)加 450 L 理鹽定容 1 mL。2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (10.95 mM); Clear soluti

5、on此案可獲得 2.5 mg/mL (10.95 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲備液加到 900 L 20% 的 SBE-CD 理鹽溶液中，混合Page 1 of 2 www.MedChemE均勻。3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (10.95 mM); Clear solution此案可獲得 2.5 mg/mL (10.95 mM，飽和度未知) 的澄 溶液，此案不適于實驗周 期在半個以上的實驗。以 1 mL 作液為例，取 100 L

6、 25.0 mg/mL 的澄 DMSO 儲備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性 Decitabine (5-Aza-2-deoxycytidine)種脫氧胞苷類似物抗代謝物 (deoxycytidine analogue antimetabolite) 和DNA 甲 轉移酶 (DNA methyltransferase) 抑制劑。Decitabine 代替 DNA 摻胞嘧啶可以將 DNA 甲基轉移酶共價捕獲到 DNA 中，從導致對該酶的不可逆抑制。Decitabine 誘導細胞 G2/M 阻滯和細胞凋亡 (apoptosis)。Decitabine

7、 具有有效的抗癌活性。IC & Target DNMT1 DNMT3A DNMT3B體外研究 Decitabine treatment significantly inhibits cell growth of SNU719, NCC24 and KATOIII 96 hours after exposure todecitabine. Decitabine induces G2/M arrest and apoptosis in EBVaGC, inhibits invasion ability, and up-regulates E-cadherin expression for EBVa

8、GC1.Only high concentrations (10 M) Decitabine (0.1-1 M; 24-72 hours) results in a G2 phase arrest, which isaccompanied by a reduction of cells in G1 phase3.Decitabine up-regulates DCTPP1 and dUTPase expression in HeLa cells4.Cell Cycle Analysis1Cell Line: HCT116 cellsConcentration: 0.1, 1, 10 MIncu

9、bation Time: 24, 48, 72 hoursResult: Only high drug concentrations (10 M) resulted in a G2 phase arrest, which wasaccompanied by a reduction of cells in G1 phase.體內研究 Decitabine (1.0 mg/kg, p.o.) in combination with tetrahydrouridine (THU) causes severe toxicity occurs in female CD-1mice, and result

10、s in an increased sensitivity to decitabine toxicity correlating with decitabine plasma levels5.Decitabine (1.0 mg/kg; i.p.; once daily for 5 consecutive days) leads to regression of EL4 tumors established inC57BL/6 Mice7.Animal Model: C57BL/6 mice (bearing EL4 cells)6Dosage: 1.0 mg/kgAdministration

11、: Intraperitoneal injection; once daily for 5 consecutive daysResult: Caused continuous tumor regression even after Decitabine treatment was stopped.戶使本產品發(fā)表的科研獻Page 2 of 3 www.MedChemE Ann Rheum Dis. 2019 Oct;78(10):1420-1429. J Allergy Clin Immunol. 2019 Jun;143(6):2038-2051.e12. Clin Chem. 2019 De

12、c;65(12):1522-1531. J Invest Dermatol. 2020 Apr 29. pii: S0022-202X(20)31390-7. Cancers (Basel). 2019 Dec 9;11(12). pii: E1984.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Nakamura M, et al. Decitabine inhibits tumor cell proliferation and up-regulates E-cadherin

13、expression in Epstein-Barr virus-associated gastric cancer. JMed Virol. 2016 Jul 19.2. Hagemann S, et al. Azacytidine and decitabine induce gene-specific and non-random DNA demethylation in human cancer cell lines. PLoS One. 2011Mar 7;6(3):e17388.3. Requena CE, et al. The nucleotidohydrolases DCTPP1

14、 and dUTPase are involved in the cellular response to decitabine. Biochem J. 2016 Jun 20.4. Terse P, et al. Subchronic oral toxicity study of decitabine in combination with tetrahydrouridine in CD-1 mice. Int J Toxicol. 2014 Mar-Apr;33(2):75-85.5. Yu J, et al. DNA methyltransferase expression in tri

15、ple-negative breast cancer predicts sensitivity to decitabine. J Clin Invest. 2018 Jun 1;128(6):2376-2388.6. Wang LX, et al. Low dose decitabine treatment induces CD80 expression in cancer cells and stimulates tumorspecific cytotoxic T lymphocyte responses.PLoS One. 2013 May 9;8(5):e62924.7. Parker WB. Enzymology of purine and pyrimidine antimetabolites used in the treatment of cancer. Chem Rev. 2009 Jul;109(7)