Abstract | PURPOSE: EXPERIMENTAL DESIGN: Human liver microsomes (HLM) and microsomes from genetically engineered cell lines expressing individual human cytochrome P450s (CYP) were used to study MMDX biotransformation. We also examined the cytotoxicity and antitumor activity of PNU-159682 using a panel of in vitro-cultured human tumor cell lines and tumor-bearing mice, respectively. RESULTS: CONCLUSIONS:
CYP3A4, the major CYP in human liver, converts MMDX to a more cytotoxic metabolite, PNU-159682, which retains antitumor activity in vivo.
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Authors | Luigi Quintieri, Cristina Geroni, Marianna Fantin, Rosangela Battaglia, Antonio Rosato, William Speed, Paola Zanovello, Maura Floreani |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 11
Issue 4
Pg. 1608-17
(Feb 15 2005)
ISSN: 1078-0432 [Print] United States |
PMID | 15746066
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- 3'-deamino-3'',4'-anhydro-(2''-methoxy-3''-oxy-4''-morpholinyl)doxorubicin
- Antineoplastic Agents
- Carbon Radioisotopes
- methoxy-morpholinyl-doxorubicin
- Doxorubicin
- Cytochrome P-450 Enzyme System
- CYP3A protein, human
- Cytochrome P-450 CYP3A
- CYP3A4 protein, human
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Topics |
- Animals
- Antineoplastic Agents
(metabolism, pharmacology)
- Carbon Radioisotopes
- Cell Line, Tumor
- Cell Survival
(drug effects)
- Chromatography, High Pressure Liquid
- Cytochrome P-450 CYP3A
- Cytochrome P-450 Enzyme System
(metabolism)
- Dose-Response Relationship, Drug
- Doxorubicin
(analogs & derivatives, chemistry, metabolism, pharmacology)
- Female
- HT29 Cells
- Humans
- Jurkat Cells
- Kinetics
- Mass Spectrometry
(methods)
- Mice
- Mice, Nude
- Microsomes, Liver
(enzymology, metabolism)
- Xenograft Model Antitumor Assays
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