Decitabine (5-Aza-2'-deoxycytidine) 是一种具有口服活性的脱氧胞苷类似物抗代谢物 (deoxycytidine analogue antimetabolite) 和 DNA 甲基转移酶 (DNA methyltransferase) 抑制剂。Decitabine 代替 DNA 掺入胞嘧啶可以将 DNA 甲基转移酶共价捕获到 DNA 中，从而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)，并具有有效的抗癌活性。
| 生物活性 | Decitabine (NSC 127716) is an orally activedeoxycytidine analogue antimetaboliteand aDNA methyltransferaseinhibitor. Decitabine incorporates into DNA in place of cytosine can covalently trapDNA methyltransferaseto DNA causing irreversible inhibition of the enzyme. Decitabine induces cell G2/M arrest and cellapoptosis. Decitabine has potent anticancer activity[1][2]. |
| IC50& Target[5] | |
体外研究
(In Vitro) | Decitabine treatment significantly inhibits cell growth of SNU719, NCC24 and KATOIII 96 hours after exposure to decitabine. Decitabine induces G2/M arrest and apoptosis in EBVaGC, inhibits invasion ability, and up-regulates E-cadherin expression for EBVaGC[1].
Only high concentrations (10 μM) Decitabine (0.1-1 μM; 24-72 hours) results in a G2 phase arrest, which is accompanied by a reduction of cells in G1 phase[3].
Decitabine up-regulates DCTPP1 and dUTPase expression in HeLa cells[4].
Cell Cycle Analysis[1] | Cell Line: | HCT116 cells | | Concentration: | 0.1, 1, 10 μM | | Incubation Time: | 24, 48, 72 hours | | Result: | Only high drug concentrations (10 μM) resulted in a G2 phase arrest, which was accompanied by a reduction of cells in G1 phase. |
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体内研究
(In Vivo) | Decitabine (1.0 mg/kg, p.o.) in combination with tetrahydrouridine (THU) causes severe toxicity occurs in female CD-1 mice, and results in an increased sensitivity to decitabine toxicity correlating with decitabine plasma levels[5].
Decitabine (1.0 mg/kg; i.p.; once daily for 5 consecutive days) leads to regression of EL4 tumors established in C57BL/6 Mice[7].
| Animal Model: | C57BL/6 mice (bearing EL4 cells)[6] | | Dosage: | 1.0 mg/kg | | Administration: | Intraperitoneal injection; once daily for 5 consecutive days | | Result: | Caused continuous tumor regression even after Decitabine treatment was stopped. |
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| 中文名称 | 地西他滨；地西他宾；2'-脱氧-5-氮杂胞啶；2'-脱氧-5-氮杂胞啶 |
| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | 4°C, protect from light *In solvent : -80°C, 6 months; -20°C, 1 month (protect from light) |
| 溶解性数据 | In Vitro: DMSO : ≥ 50 mg/mL(219.10 mM) H2O : 20 mg/mL(87.64 mM;Need ultrasonic) *"≥" means soluble, but saturation unknown. 配制储备液 | 1 mM | 4.3819 mL | 21.9096 mL | 43.8193 mL | | 5 mM | 0.8764 mL | 4.3819 mL | 8.7639 mL | | 10 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；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month (protect from light)。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方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，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；
以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂： PBS Solubility: 10 mg/mL (43.82 mM); Clear solution; Need ultrasonic 2. 请依序添加每种溶剂： 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 2.5 mg/mL (10.95 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (10.95 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。 3. 请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 2.5 mg/mL (10.95 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (10.95 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。 4. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 2.5 mg/mL (10.95 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (10.95 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。 *以上所有助溶剂都可在本网站选购。
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