5-Aza-4'-thio-2'-deoxycytidine (5-Aza-T-dCyd), a sulfur-containing deoxy-cytidine analog, serves as an orally active inhibitor of DNA methyltransferase I (DNMT1). It exhibits potential antitumor effects and DNA hypomethylating properties [1].

5-Aza-4'-thio-2'-deoxycytidine (5-Aza-T-dCyd; 72 h) effectively inhibits various leukemia lines, including CCRF-CEM (IC 50 =0.2 μM) and KG1a (IC 50 =0.06 μM). This compound also reduces the viability of several carcinoma lines, such as NCI-H23 lung carcinoma (IC 50 =4.5 μM), HCT-116 colon carcinoma (IC 50 =58 μM), and IGROV-1 ovarian carcinoma (IC 50 =36 μM) [1]. It significantly depletes DNMT1 in the NCI-H23, HCT-116, and IGROV-1 cells, as well as in CCRF-CEM and KG1a myeloid leukemia cells across various dosages (0.1-20 μM; 96 h) [1]. Furthermore, at a concentration of 1 μM and an incubation period of 96 h, 5-Aza-4'-thio-2'-deoxycytidine induces CpG demethylation and reactivates the p15 tumor suppressor gene [1]. Western blot analysis confirms that DNMT1 is markedly depleted in NCI-H23, HCT-116, and IGROV-1 cells treated with concentrations of 1, 5, 10, 20 μM for 96 h [1].

5-Aza-4'-thio-2'-deoxycytidine administered intraperitoneally at dosages of 6.7 and 10 mg/kg/day over 9 days demonstrates significant antitumor efficacy against NCI-H23 tumor xenografts in young female athymic nu/nu mice [1]. At a reduced dose of 5 mg/kg/day for the same duration, this compound effectively reduces DNMT1 levels in CCRF-CEM tumor mice xenografts [1]. Additionally, a regimen of 1.5 mg/kg given daily for five days, followed by a rest period and repeating for three cycles, achieves modest suppression in the growth of HCT116 colon carcinoma and OVCAR3 ovarian tumor xenografts. However, it exhibits minimal antitumor effects on HL-60 leukemia xenografts [2].