A new paradigm for the development of anticancer agents from natural products

Balanehru Subramanian, Alexander Nakeff, Karen Tenney, Phillip Crews, Leslie Gunatilaka, Fred Valeriote

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

A novel pharmacology paradigm has been developed which quickly and efficiently moves prospective anticancer drugs from the discovery phase through pharmacology testing and into therapeutic trial assessment. Following discovery, the drug is first assessed in a clonogenic assay which determines the cytotoxic effect of different concentrations of the drug at 3 different exposure durations: 2h, 24h and continuous (168 h). Second, pharmacokinetic information is obtained in both plasma and tumor for the drug administered at the maximum tolerated dose given intravenously. The first study defines the time-concentration profile required to obtain a specific cell survival for the tumor cells; the second study determines the concentration-time profile that can be obtained in both plasma and tumor at the maximum tolerated dose of the drug. The integration of this information determines whether a successful therapeutic trial is possible. Only when a drug shows therapeutic efficacy is a proteomics-based mechanism of action study initiated. Two drugs have been assessed in this paradigm: salicortin and fascaplysin A.

Original languageEnglish (US)
Pages (from-to)195-204
Number of pages10
JournalJournal of Experimental Therapeutics and Oncology
Volume5
Issue number3
StatePublished - Jun 14 2006

Keywords

  • Anticancer
  • Drug development
  • Fascaplysin A
  • Natural products
  • Salicortin

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Cancer Research

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  • Cite this

    Subramanian, B., Nakeff, A., Tenney, K., Crews, P., Gunatilaka, L., & Valeriote, F. (2006). A new paradigm for the development of anticancer agents from natural products. Journal of Experimental Therapeutics and Oncology, 5(3), 195-204.