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Experimental Therapeutics

Efficacy of Acylfulvene Illudin Analogues against a Metastatic Lung Carcinoma MV522 Xenograft Nonresponsive to Traditional Anticancer Agents: Retention of Activity against Various mdr Phenotypes and Unusual Cytotoxicity against ERCC2 and ERCC3 DNA Helicase-deficient Cells

Michael J. Kelner, Trevor C. McMorris, Leita Estes, Robin J. Starr, Mary Rutherford, Mark Montoya, Kyra M. Samson and Raymond Taetle
Michael J. Kelner
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Trevor C. McMorris
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Leita Estes
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Robin J. Starr
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Mary Rutherford
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Mark Montoya
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Kyra M. Samson
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Raymond Taetle
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DOI:  Published November 1995
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Abstract

Four second-generation Illudin analogues were synthesized and tested for antitumor activity using a metastatic lung carcinoma xenograft model resistant to conventional antitumor agents. One analogue, the parent illudofulvene-derivative called Acylfulvene, inhibited xenograft primary tumor growth and prolonged life span of tumor-bearing animals when administered i.p. or i.v. The efficacy of Acylfulvene exceeded that of mitomycin C, cisplatin, paclitaxol, the parent compound Illudin S, and an earlier analogue, dehydroilludin M. Promising features of this new analogue are: (a) the retention of in vitro activity against a variety of mdr tumor phenotypes including gp170+, gp150+, GSHTR-Pi, topoisomerase I, and topoisomerase II mutants; and (b) an apparent selective cytotoxicity toward cells deficient in either ERCC2 or ERCC3 DNA helicase activity.

Footnotes

  • ↵1 Supported by funds provided by the cigarette and tobacco tax fund of the State of California through the Tobacco-related Disease Research Program of the University of California Award 4RT-0226 (to M. J. K.) and by funds provided by MGI Pharma Company, Minneapolis, Minnesota (to M. J. K. and T. C. M.).

  • ↵2 To whom requests for reprints should be addressed, at Department of Pathology Mail Code 8320, UCSD Medical Center, 200 West Arbor Drive, San Diego, CA 92103.

  • Received April 10, 1995.
  • Accepted August 23, 1995.
  • ©1995 American Association for Cancer Research.
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November 1995
Volume 55, Issue 21
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Efficacy of Acylfulvene Illudin Analogues against a Metastatic Lung Carcinoma MV522 Xenograft Nonresponsive to Traditional Anticancer Agents: Retention of Activity against Various mdr Phenotypes and Unusual Cytotoxicity against ERCC2 and ERCC3 DNA Helica…
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Efficacy of Acylfulvene Illudin Analogues against a Metastatic Lung Carcinoma MV522 Xenograft Nonresponsive to Traditional Anticancer Agents: Retention of Activity against Various mdr Phenotypes and Unusual Cytotoxicity against ERCC2 and ERCC3 DNA Helicase-deficient Cells
Michael J. Kelner, Trevor C. McMorris, Leita Estes, Robin J. Starr, Mary Rutherford, Mark Montoya, Kyra M. Samson and Raymond Taetle
Cancer Res November 1 1995 (55) (21) 4936-4940;

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Efficacy of Acylfulvene Illudin Analogues against a Metastatic Lung Carcinoma MV522 Xenograft Nonresponsive to Traditional Anticancer Agents: Retention of Activity against Various mdr Phenotypes and Unusual Cytotoxicity against ERCC2 and ERCC3 DNA Helicase-deficient Cells
Michael J. Kelner, Trevor C. McMorris, Leita Estes, Robin J. Starr, Mary Rutherford, Mark Montoya, Kyra M. Samson and Raymond Taetle
Cancer Res November 1 1995 (55) (21) 4936-4940;
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