Isofistularin-3, a direct DNA-competitive DNMT1 inhibitor with an IC50 of 13.5 μM, functions as a DNA demethylating agent, leading to cell cycle arrest and increased sensitivity to TRAIL in cancer cells. Additionally, it can be employed as an ADC cytotoxin.

DNMT1:13.5 μM

Isofistularin-3 (72 hours) inhibits a broader panel of cancer cell lines proliferation, with the GI50s ranging from 7.3-14.8 μM. Isofistularin-3 induces morphological changes and autophagy in RAJI cells. Isofistularin-3 induces caspase-dependent and -independent cell death. Isofistularin-3 sensitizes lymphoma cells to TRAIL-induced apoptosis.Isofistularin-3 (1-50 μM; 24-72 hours) shows a marked reduction of cell proliferation. Isofistularin-3 (5-50 μM; 24 hours) increases arrests cancer cells in G0/G1 cell cycle phase. Isofistularin-3 (25 μM; 72 hours) increases AHR expression. Isofistularin-3 induces AHR promoter demethylation.