Hydroxyrubicin is an antitumor drug that induces DNA breaks at the human c-myc initiation site through topoisomerase II mediation and can cause DNA unwinding. It significantly inhibits tumor cells and is applicable in research on multidrug-resistant (MDR) leukemia.

Hydroxyrubicin, at concentrations of 1-10 μM for 30 minutes, can induce topoisomerase II-mediated DNA breakage in human c-myc initiator DNA. At 2.5-10 μM over the same duration, it causes concentration-dependent DNA unwinding. In sensitive KB3.1 cells, Hydroxyrubicin exhibits slightly greater cytotoxicity than doxorubicin with IC 50 values of 0.35 μM versus 0.8 μM, and in KB-V1 cells, its cytotoxicity is 20 times that of doxorubicin (IC 50 of 2 μM compared to 40 μM). In both KB3.1 and KB-V1 cells, accumulation of Hydroxyrubicin (0-10 μM for 1 hour) exceeds that of doxorubicin (5 times higher in KB3.1 and 2 times higher in KB-V1); however, in resistant cells, Hydroxyrubicin accumulates 6-7 times less than in sensitive cells. Compared to doxorubicin, Hydroxyrubicin (0-10 μM) induces slightly more DNA single-strand breaks (SSB) and DNA-protein crosslinks (DPC), with protein cross-linker breaks observed in both KB3.1 and KB-V1 cells.

Administered intravenously at doses ranging from 25 to 79.1 mg/kg once per week for 11 weeks, Hydroxyrubicin significantly reduces acute and cardiac toxicity in mice by removing the C-3' amino group from doxorubicin, while maintaining its antitumor efficacy in the P388/Dox cell xenograft mouse model.