地西他濱作用機(jī)制 - Medchemexpress - MCE中國(guó)

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

2、體外實(shí)驗(yàn) DMSO : 50 mg/mL (219.10 mM)* means soluble, but saturation unknown.SolventMass1 mg 5 mg 10 mgConcentration制備儲(chǔ)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(qǐng)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(chǔ)備液；旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存式和期限：-80C, 6 months

3、; -20C, 1 month (protect from light)。-80C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?6 個(gè)內(nèi)使，-20C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?1 個(gè)內(nèi)使。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍?。以下溶解案都?qǐng)先按照 In Vitro 式配制澄清的儲(chǔ)備液，再依次添加助溶劑：為保證實(shí)驗(yàn)結(jié)果的可靠性，澄 的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)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(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)加熱和/或超聲的式助溶1. 請(qǐng)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(chǔ)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(qǐng)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(chǔ)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(qǐng)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(shí)驗(yàn)周 期在半個(gè)以上的實(shí)驗(yàn)。以 1 mL 作液為例，取 100 L

6、 25.0 mg/mL 的澄 DMSO 儲(chǔ)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(zhuǎn)移酶 (DNA methyltransferase) 抑制劑。Decitabine 代替 DNA 摻胞嘧啶可以將 DNA 甲基轉(zhuǎn)移酶共價(jià)捕獲到 DNA 中，從導(dǎo)致對(duì)該酶的不可逆抑制。Decitabine 誘導(dǎo)細(xì)胞 G2/M 阻滯和細(xì)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(nèi)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(chǎn)品發(fā)表的科研獻(xiàn)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)