MC3817

MC3817 is a selective DNMT1 inhibitor. MC3817 inhibits DNMT1 and DNMT3A/3L with IC₅₀ s of 0.044 μM and > 10μM, respectively. MC3817 inhibits P53-dependent cancer cell proliferation, induces apoptosis and DNA damage MC3817 elevates cleaved Caspase 3, P53, and γH2AX. MC3817 can be used in non-small cell lung cancer, colon cancer, cervical cancer, triple-negative breast cancer and histiocytic lymphoma research ^[1].

In Vitro, MC3817 (compound 14) (0.05-100 μM, 48 h) exhibits antiproliferative activity against A549 and H460 (non-small cell and lung cancer), HCT-116 (colon cancer), HeLa (cervical cancer), MDA-MB-231 (triple-negative breast cancer), and U937 (histiocytic lymphoma) cells^[1]. MC3817 (2 μM, 24 and 48 h) induces S/G2M phase arrest and triggers apoptotic cell death in HCT-116 cells^[1]. MC3817 (0.5-5 μM, 16-48 h) triggers DNA damage and activates the p53/γH2AX pathway, leading to cell-cycle arrest and apoptosis in HCT 116 cells^[1]. MC3817 (2.5 μM, 48 h) induces a much higher level of apoptosis in HCT-116 P53 WT cells compared with HCT-116 P53−/− cells ^[1].

References:
[1]. Zwergel C, et al. Quinoline-Based DNA Methyltransferase Inhibitors Featuring Basic Side Chains: Design, Synthesis, and Insight in Biochemical and Anticancer Cell Properties. J Med Chem. 2025 Nov 27;68(22):23886-23909.