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.

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.
Authors	M J Kelner, T C McMorris, L Estes, R J Starr, M Rutherford, M Montoya, K M Samson, R Taetle
Journal	Cancer research (Cancer Res) Vol. 55 Issue 21 Pg. 4936-40 (Nov 01 1995) ISSN: 0008-5472 [Print] United States
PMID	7585533 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Antibiotics, Antineoplastic DNA-Binding Proteins Drosophila Proteins Proteins Sesquiterpenes Transcription Factors hay protein, Drosophila DNA Helicases Xeroderma Pigmentosum Group D Protein Ercc2 protein, mouse
Topics	Adenocarcinoma (drug therapy, metabolism) Animals Antibiotics, Antineoplastic (pharmacology) DNA Helicases (deficiency) DNA Repair DNA-Binding Proteins (metabolism) Disease Models, Animal Drosophila Proteins Drug Resistance, Neoplasm Drug Screening Assays, Antitumor Female Lung Neoplasms (drug therapy, metabolism) Mice Mice, Inbred BALB C Mice, Nude Neoplasm Metastasis Neoplasm Transplantation Phenotype Proteins (metabolism) Sesquiterpenes (pharmacology) Transcription Factors Transplantation, Heterologous Xeroderma Pigmentosum Group D Protein

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!