A DNA methyltransferase inhibitor
5-Azacytidine (also known as 5-AzaC), a compound belonging to a class of cytosine analogues, is a DNA methyl transferase (DNMT) inhibitor that exerts potent cytotoxicity against multiple myeloma (MM) cells, including MM.1S, MM.1R, RPMI-8266, RPMI-LR5, RPMI-Dox40 and Patient-derived MM, with the half maximal inhibition concentration IC50 values of 1.5 μmol/L, 0.7 μmol/L, 1.1 μmol/L, 2.5 μmol/L, 3.2 μmol/L and 1.5 μmol/L respectively [1].
5-Azacytidine incorporates into cellular DNA and/or RNA, subsequently sequesters DNMT and forms a covalent bond between C6 of 5-Azacytidine and cysteine thiolate of DNMTs resulting in depletion of DNMT activity in cells and demethylation of cellular DNA [1].
参考文献:
[1] Kiziltepe T, Hideshima T, Catley L, Raje N, Yasui H, Shiraishi N, Okawa Y, Ikeda H, Vallet S, Pozzi S, Ishitsuka K, Ocio EM, Chauhan D, Anderson KC. 5-Azacytidine, a DNA methyltransferase inhibitor, induces ATR-mediated DNA double-strand break responses, apoptosis, and synergistic cytotoxicity with doxorubicin and bortezomib against multiple myeloma cells. Mol Cancer Ther. 2007 Jun;6(6):1718-27.
5-氮胞苷（也称为 5-AzaC）是一类胞嘧啶类似物的化合物，是一种 DNA 甲基转移酶 (DNMT) 抑制剂，对多发性骨髓瘤 (MM) 细胞（包括 MM.1S）具有强效细胞毒性, MM.1R, RPMI-8266, RPMI-LR5, RPMI-Dox40和Patient-derived MM,半数抑制浓度IC50值分别为1.5 μmol/L, 0.7 μmol/L, 1.1 μmol/L, 2.5 μmol/L , 分别为 3.2 μmol/L 和 1.5 μmol/L [1].
5-氮胞苷掺入细胞 DNA 和/或 RNA，随后螯合 DNMT 并在 5-氮胞苷的 C6 和半胱氨酸之间形成共价键DNMT 的硫醇盐导致细胞中 DNMT 活性的耗竭和细胞 DNA 的去甲基化 [1]。
| Cell experiment [1]: | |
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Cell lines |
Leukemia L1210 cells |
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Preparation method |
The solubility of this compound in DMSO is > 12.2 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
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Reacting condition |
80 μM; 0 ~ 120 mins |
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Applications |
In leukemia L1210 cells, 5-Azacytidine showed greater inhibition on DNA synthesis instead of RNA synthesis. After a 90-min preincubation, TdR-3H incorporation was inhibited by about 74%, whilst UR-3H incorporation was inhibited by only 32%. |
| Animal experiment [2]: | |
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Animal models |
BDF1 mice bearing lymphoid leukemia L1210 cells |
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Dosage form |
3 mg/kg; i.p.; q.d. |
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Applications |
In BDF1 mice bearing lymphoid leukemia L1210 cells, 5-Azacytidine increased the mean survival time. Moreover, 5-Azacytidine significantly suppressed all enzymes activity in the polyamine-biosynthetic pathway. In addition, 5-Azacytidine inhibited accumulation of polyamines in leukemic mice. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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参考文献: [1]. Li LH, Olin EJ, Buskirk HH, Reineke LM. Cytotoxicity and mode of action of 5-azacytidine on L1210 leukemia. Cancer Res. 1970 Nov;30(11):2760-9. [2]. Heby O, Russell DH. Depression of polyamine synthesis in L1210 leukemic mice during treatment with a potent antileukemic agent, 5-azacytidine. Cancer Res. 1973 Jan;33(1):159-65. |
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