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Discovery and development of anticancer agents from marine sponges: perspectives based on a chemistry-experimental therapeutics collaborative program
Journal of Experimental Therapeutics and Oncology (2012)
  • Frederick A. Valeriote, Henry Ford Health System
  • Karen Tenney, University of California, Santa Cruz
  • Joseph Media, Henry Ford Health System
  • Halina Pietraszkiewicz, Henry Ford Health System
  • Matthew Edelstein, Henry Ford Health System
  • Tyler A. Johnson, University of California, Santa Cruz
  • Taro Amagata, University of California, Santa Cruz
  • Phillip Crews, University of California, Santa Cruz
Abstract
A collaborative program was initiated in 1990 between the natural product chemistry laboratory of Dr. Phillip Crews at the University of California Santa Cruz and the experimental therapeutics laboratory of Dr. Fred Valeriote at the Henry Ford Hospital in Detroit. The program focused on the discovery and development of anticancer drugs from sponge extracts. A novel in vitro disk diffusion, solid tumor selective assay was used to examine 2,036 extracts from 683 individual sponges.The bioassay-directed fractionation discovery component led to the identification of active pure compounds from many of these sponges.In most cases, pure compound was prepared in sufficient quantities to both chemically identify the active compound(s) as well as pursue one or more of the biological development components. The latter included IC50, clonogenic survival-concentration exposure, maximum tolerated dose, pharmacokinetics and therapeutic assessment studies. Solid tumor selective compounds included tascaplysin and 10-bromofascaplysin (Fascapiysinopsis), neoamphimedine, 5-methoxyneoamphimedine and alpkinidine (Xestospongia), makaluvamine C and makaluvamine H (Zyzzya), psymberin {Psammociniaar\á ircinia), and ethylplakortide Z and ethyldidehydropiakortide Z {Plai<ortis). These compounds or analogs thereof continue to have therapeutic potential.
Keywords
  • Anticancer drugs,
  • natural products,
  • marine sponges
Publication Date
2012
Citation Information
Frederick A. Valeriote, Karen Tenney, Joseph Media, Halina Pietraszkiewicz, et al.. "Discovery and development of anticancer agents from marine sponges: perspectives based on a chemistry-experimental therapeutics collaborative program" Journal of Experimental Therapeutics and Oncology Vol. 10 (2012) p. 119 - 134 ISSN: 1359-4117
Available at: http://works.bepress.com/tyler-a-johnson/23/