Abstract |
Resistance to the classical anthracyclines may be due to one or several mechanisms, most notably p-glycoprotein (pGP) associated multidrug resistance (mdr1, "typical mdr") and altered activity of topoisomerase II ( topo II) ("atypical mdr"). Modulators of mdr1 will be of limited value in case of combined forms of resistance. A Friend murine erythroleukemia cell line (F4-6R) carrying both mdrl and topo II mediated anthracycline resistance was used to determine the efficacy of structurally altered anthracyclines against such extended multidrug resistance. Proliferation assays showed that 3'N-morpholinyl substituted anthracyclines were able to retain much of their activity even in this setting. MX2 (KRN8602; 3'-deamino-3'-[4-morpholinyl]-13-deoxo-10-hydroxycarminomycin+ ++), which is 9-alkylated in addition to carrying a 3'N-morpholinyl group, was the most promising agent tested.
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Authors | S S Bielack, K Kallenbach, G Looft, R Erttmann, K Winkler |
Journal | Anticancer research
(Anticancer Res)
1995 Jul-Aug
Vol. 15
Issue 4
Pg. 1279-84
ISSN: 0250-7005 [Print] Greece |
PMID | 7654009
(Publication Type: Journal Article)
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Chemical References |
- Antibiotics, Antineoplastic
- DNA Topoisomerases, Type II
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Topics |
- Animals
- Antibiotics, Antineoplastic
(pharmacology)
- Cell Division
(drug effects)
- DNA Topoisomerases, Type II
(metabolism)
- Drug Resistance, Multiple
- Leukemia, Erythroblastic, Acute
(pathology)
- Mice
- Structure-Activity Relationship
- Tumor Cells, Cultured
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