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Activity of the morpholino anthracycline 3′-deamino-3′-morpholino-13-deoxo-10-hydroxycarminomycin (MX2) against human tumor colony-forming unitsin vitro

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Summary

In several preclinical systems, the morpholino anthracycline MX2 has greater antitumor activity than doxorubicin, is less cardiotoxic, and is effective against multidrug resistant cancer cells. We used a human tumor soft-agar cloning assay to test the cytotoxicity of MX2 against single cell suspensions from freshly obtained human tumors. Tumor cells were exposed to MX2 at 0.05 and 0.5 μg/ml either for 1 hour (201 specimens; 77 [38%] assessable) or continuously (231 specimens; 91 [39%] assessable). Superior antitumor activity was observed with continuous exposure (19%in vitro response at 0.05 μg/ml and 69% at 0.5 μg/ml) than with 1-hour exposure (1.3% at 0.05 μg/ml and 12% at 0.5 μg/ml). Activity was seen against all types of cancer tested including renal (91%), melanoma (88%), ovarian (73%), breast (71%) and non-small-cell lung (67%) cancer at a MX2 concentration of 0.5 μg/ml after continuous exposure. If appropriate plasma levels can be achieved in patients, MX2 could have significant clinical activity in patients with those tumors.

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Authors and Affiliations

  1. Dept. of Experimental Pathology, New York Medical College, 10595, Valhalla, NY

    A. A. Ebrahim El-Zayat

  2. Cancer Therapy & Research Center, 8122 Datapoint Dr., Suite 700, 78229, San Antonio, TX

    Miguel A. Izquierdo & Daniel D. Von Hoff

  3. University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA

    G. M. Clark

Authors
  1. A. A. Ebrahim El-Zayat
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  2. Miguel A. Izquierdo
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  3. G. M. Clark
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  4. Daniel D. Von Hoff
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Ebrahim El-Zayat, A.A., Izquierdo, M.A., Clark, G.M. et al. Activity of the morpholino anthracycline 3′-deamino-3′-morpholino-13-deoxo-10-hydroxycarminomycin (MX2) against human tumor colony-forming unitsin vitro . Invest New Drugs 13, 125–131 (1995). https://doi.org/10.1007/BF00872860

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