The research team focused on triple-negative breast cancer (TNBC), a particularly difficult-to-treat form of breast cancer that does not respond to many standard targeted therapies. In cellular experiments, DHL-11 simultaneously inhibited the proliferation of cancer cells, reduced their migration ability, and halted the cell cycle in the G2/M phase, ultimately leading to apoptosis – programmed cell death.
The compound’s key mechanism of action involves disrupting the function of the enzyme IMPDH2, which plays an important role in cancer cell metabolism. DHL-11 does not directly block the enzyme’s active site but instead binds to another region of the protein and interferes with its interaction with the FANCI protein. This leads to degradation of IMPDH2, reduced guanine synthesis, and increased levels of reactive oxygen species inside the cell. As a result, cancer cells experience intense oxidative stress and DNA damage that they are unable to repair.
Researchers confirmed the compound’s activity in more complex experimental models. DHL-11 significantly inhibited the growth of tumor organoids derived from patients, which retain many characteristics of real tumors. In animal experiments involving transplanted TNBC tumors, the compound suppressed both tumor growth and metastasis while demonstrating a favorable biological safety profile.
The authors emphasize that the discovery may open a new direction in cancer therapies targeting cellular metabolism. Of particular interest is the possibility of using IMPDH2 degradation as a therapeutic target in breast cancers with high expression of this enzyme.
At this stage, however, the research remains at the preclinical level. Scientists note that the next steps will involve further testing in animal models and evaluating potential effectiveness against other cancer types before clinical trials in humans can begin.