地西他滨作用机制 - Medchemexpress - MCE中国

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

2、体外实验 DMSO : 50 mg/mL (219.10 mM)* means soluble, but saturation unknown.SolventMass1 mg 5 mg 10 mgConcentration制备储备液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请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存式和期限：-80C, 6 months

3、; -20C, 1 month (protect from light)。-80C 储存时，请在 6 个内使，-20C 储存时，请在 1 个内使。体内实验请根据您的实验动物和给药式选择适当的溶解案。以下溶解案都请先按照 In Vitro 式配制澄清的储备液，再依次添加助溶剂：为保证实验结果的可靠性，澄 的储备液可以根据储存条件，适当保存；体内实验的作液，建议您现现配，当天使； 以下溶剂前显的百分 指该溶剂在您配制终溶液中的体积占；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的式助溶1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% s

4、alineSolubility: 2.5 mg/mL (10.95 mM); Clear solution此案可获得 2.5 mg/mL (10.95 mM，饱和度未知) 的澄清溶液。以 1 mL 作液为例，取 100 L 25.0 mg/mL 的澄 DMSO 储备液加到 400 L PEG300 中，混合均匀；向上述体系中加50 L Tween-80，混合均匀；然后继续加 450 L 理盐定容 1 mL。2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (10.95 mM); Clear soluti

5、on此案可获得 2.5 mg/mL (10.95 mM，饱和度未知) 的澄清溶液。以 1 mL 作液为例，取 100 L 25.0 mg/mL 的澄 DMSO 储备液加到 900 L 20% 的 SBE-CD 理盐溶液中，混合Page 1 of 2 www.MedChemE均匀。3. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (10.95 mM); Clear solution此案可获得 2.5 mg/mL (10.95 mM，饱和度未知) 的澄 溶液，此案不适于实验周 期在半个以上的实验。以 1 mL 作液为例，取 100 L

6、 25.0 mg/mL 的澄 DMSO 储备液加到 900 L 油中，混合均匀。BIOLOGICAL ACTIVITY物活性 Decitabine (5-Aza-2-deoxycytidine)种脱氧胞苷类似物抗代谢物 (deoxycytidine analogue antimetabolite) 和DNA 甲 转移酶 (DNA methyltransferase) 抑制剂。Decitabine 代替 DNA 掺胞嘧啶可以将 DNA 甲基转移酶共价捕获到 DNA 中，从导致对该酶的不可逆抑制。Decitabine 诱导细胞 G2/M 阻滞和细胞凋亡 (apoptosis)。Decitabine

7、 具有有效的抗癌活性。IC & Target DNMT1 DNMT3A DNMT3B体外研究 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.体内研究 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.户使本产品发表的科研献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)