ED-110, a novel indolocarbazole, prevents the growth of experimental tumors in mice.

A new indolocarbazole compound, ED-110, which was obtained by glucosylating a microbial product (BE-13793C) and is a potent topoisomerase I inhibitor, showed characteristic inhibitory effects on the growth of 12 human tumor cell lines tested. The IC50 values of ED-110 against 9 of the 12 lines ranged from 11.5 micrograms/ml to 0.07 microgram/ml, while the remaining 3 lines were quite resistant (IC50, > 100 micrograms/ml). In in vivo experiments, i.p. treatment with ED-110 increased the survival period by more than two-fold in mice implanted i.p. with P388, L1210, L5178Y or EL4 murine leukemic cells. The minimum effective dose increasing the life-span of mice bearing P388 leukemia by 25% was < 2.5 mg/kg/day x 10 and the maximum tolerated dose was > 160 mg/kg/day x 10. ED-110 was also effective against the spontaneous metastasis of mouse Meth A fibrosarcoma cells and the growth of xenografted MKN-45 human stomach cancer cells as well as s.c. implanted mouse colon 26 and IMC carcinoma cells. These results indicated that ED-110 may have potential as a new antineoplastic agent with a large chemotherapeutic index and a wide range of effective doses.