title: Activity of the morpholino anthracycline 3'-deamino-3'-morpholino-13-deoxo-10-hydroxycarminomycin (MX2) against human tumor colony-forming units in vitro.
abstract: 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 micrograms/ml either for 1 hour (2-1 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 micrograms/ml and 69% at 0.5 micrograms/ml) than with 1-hour exposure (1.3% at 0.05 micrograms/ml and 12% at 0.5 micrograms/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 micrograms/ml after continuous exposure. If appropriate plasma levels can be achieved in patients, MX2 could have significant clinical activity with those tumors.
authors.affiliation: Dept. of Experimental Pathology, New York Medical College, Valhalla 10595, USA.
authors.forename: A A
authors.initials: AA
authors.lastname: Ebrahim el-Zayat
authors.forename: M A
authors.initials: MA
authors.lastname: Izquierdo
authors.forename: G M
authors.initials: GM
authors.lastname: Clark
authors.forename: D D
authors.initials: DD
authors.lastname: Von Hoff
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002360:Carubicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D018432:Drug Resistance, Multiple; D015507:Drugs, Investigational / Q000494:pharmacology*; D006801:Humans; D009369:Neoplasms / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
chemical_list: D000903:Antibiotics, Antineoplastic; D015507:Drugs, Investigational; C053537:morpholinoanthracycline MX2; D002360:Carubicin