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MX2, a Morpholino Anthracycline, as a New Antitumor Agent against Drug-sensitive and Multidrug-resistant Human and Murine Tumor Cells¹

Pharmaceutical Laboratory, Kirin Brewery Co., Ltd., Maebashi, Gunma 371 [M. W., N. K., S. N.]; and Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Kami-Ikebukuro, Toshima-ku, Tokyo 170 [T. T.]; Japan

MX2, a new morpholino anthracycline, showed similar or superior chemotherapeutic effects to Adriamycin (ADM) against several experimental murine tumors. i.v. administration of MX2 against L1210-bearing mice induced a prolongation of life-span by twice or more compared to ADM. MX2 was equally or slightly more effective against Lewis lung carcinoma and colon adenocarcinomas 26 and 38 than ADM when either drug was given i.v. The antitumor activity of MX2 against human tumor xenografts was similar to that of ADM, and the compound was effective against three out of four gastric adenocarcinomas, one out of two non-small-cell lung carcinomas, and two out of two mammary adenocarcinomas. In particular, this compound exhibited a marked effect against MX-1, a human mammary adenocarcinoma. MX2, in contrast to ADM, was effective against sublines of P388 leukemia resistant to ADM or aclacinomycin A in vivo as well as in vitro. A maximum percentage increase in life-span of about 90% was obtained in mice bearing these resistant tumors. MX2 is a unique anthracycline antibiotic effective on drug-sensitive as well as multidrug-resistant murine and human cells.

¹ Supported by a Grant-in-Aid for Cancer Research from the Ministry of Education, Science and Culture, Japan.

² To whom requests for reprints should be addressed.

Received 5/ 2/88. Revised 8/19/88. Accepted 8/29/88.

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