一种新型抗肿瘤抗生素，FR-900482。III. 对可移植性实验肿瘤的抗肿瘤活性。

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

作者信息

Shimomura K, Hirai O, Mizota T, Matsumoto S, Mori J, Shibayama F, Kikuchi H

出版信息

J Antibiot (Tokyo). 1987 May;40(5):600-6. doi: 10.7164/antibiotics.40.600.

DOI:10.7164/antibiotics.40.600

Abstract

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.

摘要

FR - 900482（4 - 甲酰基 - 6,9 - 二羟基 - 14 - 氧杂 - 1,11 - 二氮杂四环[7.4.1.02,7, O10,12]十四碳 - 2,4,6 - 三烯 - 8 - 基甲基氨基甲酸酯）是从三田链霉菌发酵液中分离出的一种具有抗肿瘤活性的新型抗生素。对其抗肿瘤活性进行了研究，并在动物体内与丝裂霉素C（MMC）进行了比较。剂量为0.32至10mg/kg（腹腔注射）的FR - 900482可延长携带腹水型P388、L1210、B16、MM46、艾氏或EL4肿瘤的小鼠以及携带腹水型AH130或AMC60肿瘤的大鼠的生存期。剂量为5.6至18mg/kg（静脉注射）的FR - 900482可抑制裸鼠皮下移植的人LX - 1、MX - 1、SC - 6和LC - 6肿瘤。在所有使用的肿瘤模型中，FR - 900482比MMC更有效或与之效果相当。FR - 900482对环磷酰胺耐药的P388无效，但对MMC或长春新碱耐药的P388有效。结果表明FR - 900482可能具有临床应用潜力。