A new antitumor antibiotic, FR-900482. III. Antitumor activity in transplantable experimental tumors

FR-900482 (4-formyl-6,9-dihydroxy-14-oxa-1,11-diazatetracyclo[7.4.1.02,7, O10,12]tetradeca-2,4,6-triene-8-ylmethyl carbamate), a new antibiotic with antitumor activity was isolated from fermentation broth of Streptomyces sandaensis. Its antitumor activities were studied and compared with that of mitomycin C (MMC) in animals. FR-900482 in doses of 0.32 approximately 10 mg/kg (ip) prolonged the life of mice bearing ascitic P388, L1210, B16, MM46, Ehrlich or EL4 tumors and rats bearing ascitic AH130 or AMC60 tumors. FR-900482 in doses of 5.6 approximately 18 mg/kg (iv) inhibited human LX-1, MX-1, SC-6 and LC-6 tumors xenografted sc in nude mice. FR-900482 was more effective than or equally effective to MMC in all the tumors used. FR-900482 was ineffective against cyclophosphamide-resistant P388, but was effective against MMC- or vincristine-resistant P388. The results suggest that FR-900482 may have clinical potential.