Anticanceragent 289 is an H2O2-responsive anticancer prodrug. It demonstrates H2O2-induced DNA alkylation activity and selectively inhibits the proliferation of cancer cells with high ROS expression, compared to non-malignant cells. It significantly suppresses tumor growth in vivo without visible toxicity. Anticanceragent 289 is applicable for research in triple-negative breast cancer (TNBC).

Anticancer agent 289 (compound 10a) demonstrates preferential cytotoxicity towards MDA-MB-468 cells with an IC50 of 5.1 μM, while exhibiting lower toxicity against MCF-10A cells, with an IC50 of 16.2 μM, approximately three times higher. It shows good aqueous solubility (74 μM) and moderate permeability at physiological pH 7.4 (logPe = −5.67), with enhanced passive diffusion capability under acidic conditions (logPe increases slightly to -5.22 at pH 6.4).

Anticancer agent 289 (compound 10a) administered at 5.0 mg/kg via daily intraperitoneal injection for 8 weeks demonstrates selective tumor inhibition in an MDA-MB-468 cell-induced xenograft mouse model, while not affecting normal tissue, indicating notable antitumor activity and safety. When Anticancer agent 289 is given at 15 mg/kg as a single intraperitoneal injection combined with its precise deuterated analogue, it maintains good safety in the same mouse model and minimizes off-target effects.