5-Aza-4'-thio-2'-deoxycytidine

5-Aza-4'-thio-2'-deoxycytidine (5-Aza-T-dCyd) is an orally active DNA methyltransferase I (DNMT1) inhibitor. 5-Aza-4'-thio-2'-deoxycytidine, a sulfur-containing deoxy-cytidine analog, has the potential for DNA hypomethylating and has antitumor effects[1].

Research Areas >> Cancer

Signaling Pathways >> Epigenetics >> DNA Methyltransferase

DNMT1

5-Aza-4'-thio-2'-deoxycytidine (5-Aza-T-dCyd; 72 h) inhibits leukemia lines: CCRF-CEM (IC50=0.2 μM), KG1a (IC50=0.06 μM). 5-Aza-4'-thio-2'-deoxycytidine also decreases viability in the NCI-H23 lung carcinoma (IC50=4.5 μM), HCT-116 colon carcinoma (IC50=58 μM) and IGROV-1 ovarian carcinoma (IC50=36 μM)[1]. 5-Aza-4'-thio-2'-deoxycytidine (0.1-20 μM; 96 h) markedly depletes DNMT1 in NCI-H23 lung, HCT-116 colon and IGROV-1 ovarian cells. 5-Aza-4'-thio-2'-deoxycytidine (0.1, 0.5, 1 μM; 96 h) results in marked depletion of DNMT1 in CCRF-CEM and KG1a myeloid leukemia cells[1]. 5-Aza-4'-thio-2'-deoxycytidine (1 μM; 96 h) induce CpG demethylation and re-expression of the p15 tumor suppressor gene[1]. Western Blot Analysis[1] Cell Line: NCI-H23 lung, HCT-116 colon and IGROV-1 ovarian cells Concentration: 1, 5, 10, 20 μM Incubation Time: 96 h Result: Markedly depleted DNMT1 in cells.

5-Aza-4'-thio-2'-deoxycytidine (6.7, 10 mg/kg/day; IP; for 9 days) is effective against NCI-H23 tumor xenografts[1]. 5-Aza-4'-thio-2'-deoxycytidine (5 mg/kg/day; IP; for 9 days) decreases DNMT1 levels in tumors of CCRF-CEM tumors mice xenografts[1]. 5-Aza-4'-thio-2'-deoxycytidine (1.5 mg/kg; ip; QD×5 rest and repeat 3 cycles) provides modest suppression of tumor growth as well in the HCT116 colon carcinoma, OVCAR3 ovarian tumor xenograft model. 5-Aza-4'-thio-2'-deoxycytidine has minimal antitumor effect in the HL-60 leukemia xenografts[2]. Animal Model: Young female athymic nu/nu mice with NCI-H23 tumor fragment[1] Dosage: 6.7 or 10 mg/kg Administration: IP; daily for 9 days Result: Had antitumor efficacy against NCI-H23 tumor xenografts.

[1]. Jaideep V Thottassery, et al. Novel DNA methyltransferase-1 (DNMT1) depleting anticancer nucleosides, 4'-thio-2'-deoxycytidine and 5-aza-4'-thio-2'-deoxycytidine. Cancer Chemother Pharmacol. 2014 Aug;74(2):291-302.

[2]. Joel Morris, et al. F-aza-T-dCyd (NSC801845), a Novel Cytidine Analog, in Comparative Cell Culture and Xenograft Studies with the Clinical Candidates T-dCyd, F-T-dCyd, and Aza-T-dCyd. Mol Cancer Ther. 2021 Apr;20(4):625-631.