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].
References:
[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]。