Drug development from marine natural products

Abstract

Drug discovery from marine natural products has enjoyed a renaissance in the past few years. Ziconotide (Prialt; Elan Pharmaceuticals), a peptide originally discovered in a tropical cone snail, was the first marine-derived compound to be approved in the United States in December 2004 for the treatment of pain. Then, in October 2007, trabectedin (Yondelis; PharmaMar) became the first marine anticancer drug to be approved in the European Union. Here, we review the history of drug discovery from marine natural products, and by describing selected examples, we examine the factors that contribute to new discoveries and the difficulties associated with translating marine-derived compounds into clinical trials. Providing an outlook into the future, we also examine the advances that may further expand the promise of drugs from the sea.

Key Points

  • The large-scale collection, screening and discovery of novel marine natural products has propelled new chemical entities into the clinic for the treatment of pain, cancer and other disease states.

  • What is the status of discovery of 'drugs from the sea' and what hope do they offer for the alleviation of human suffering? The first two new drugs derived from marine organisms have now been approved — one for cancer and the other for chronic pain.

  • Other natural-product-inspired drugs, such as the anticancer compound eribulin mesylate, are in the pipeline.

  • We present the history and current stage of development for a selection of marine natural products, and examine the obstacles in their development into drugs.

  • We also discuss how new technologies in analytical sciences and 'genomic mining' are accelerating the pace of discovery.

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Figure 1: ω-conotoxin MVIIA.
Figure 2: Marine invertebrates producing anticancer and analgesic drugs.
Figure 3: Tunicate-derived anticancer drugs.
Figure 4: Molecular-dynamics model showing the alkylation of DNA by ET-743 at N2 of guanine in the minor groove.
Figure 5: Marine-derived antimitotic compounds (part 1).
Figure 6: Marine-derived antimitotic compounds (part 2).
Figure 7: Kahalalide F and bryostatins.

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Acknowledgements

The authors are grateful to J. Blunt (University of Canterbury, New Zealand) and D. Newman (Developmental Therapeutics Program, US National Cancer Institute) for valuable discussions, and to S. Lopez-Legintil (University of North Carolina, Wilmington, USA) for kind permission to reproduce the underwater image of Ecteinascidia turbinata (figure 2b). Some of the authors' research described herein was supported by grants to T.F.M. from the US National Cancer Institute, National Institutes of Health (CA122256 and CA085602).

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