The future of plant drug discovery

John Littleton

Research output: Contribution to journalReview articlepeer-review

11 Scopus citations

Abstract

To have a future in the pharmaceutical industry, plant drug discovery must compete with combinatorial chemistry and high-throughput pharmacologic screening (HTPS). Plant functional genomics coupled with HTPS may achieve this; thus, functional biology can identify 'libraries' of candidate plant species from which individuals can be prioritized by 'differential HTPS'. The full genomic potential of a species for bioactivity can be accessed by cellular mutagenesis and elicitation, with HTPS identifying clones with novel activity. The comparison of 'positive' clonal phenotypes with their almost identical 'negatives' facilitates the identification of active compounds and 'genomic' products. The logical conclusion is to use combinatorial genomics together with HTPS to direct plant cellular 'evolution' continuously towards metabolites with specific pharmacologic activity. Mankind would then become the orchestrator of plant secondary metabolism, rather than its passive beneficiary.

Original languageEnglish
Pages (from-to)673-683
Number of pages11
JournalExpert Opinion on Drug Discovery
Volume2
Issue number5
DOIs
StatePublished - May 2007

Bibliographical note

Funding Information:
Several colleagues have contributed to the author’s education and to these ideas, most notably D Falcone (plant molecular biology) and T Rogers (high-throughput screening of plant extracts). M Davies (Director of the Kentucky Tobacco Research and Development Center [KTRDC]) has encouraged the research throughout and additional input has come from P Crooks (natural product chemistry) and P Lawless (plant evolutionary biology). Funding is acknowledged from KTRDC, Kentucky Science and Technology Corporation and from NIH (RO1AA012600, R41AA014555, R41AA4554, R41AA015475, R41CA115093).

Keywords

  • Elicitation
  • Evolution
  • Genomics
  • Mutagenesis
  • Pharmacology
  • Screening
  • Secondary metabolism

ASJC Scopus subject areas

  • Drug Discovery

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