Therapeutic potential of natural product signal transduction agents.
Modern drug discovery embraces a strategy of targeting cellular signal transduction pathways as a means of finding new therapeutic agents. Historically, natural products derived from microorganisms have played an important role as drug leads and clinical candidates under this paradigm. The future drug potential of natural products as signal transduction agents looks promising, as illustrated by two key examples. First, substantial advances have been made in the development of inhibitors based on immunophilin ligand polyketides, which target the TOR-mediated pathways and can modulate processes including cell proliferation and cell-cycle arrest. Second, the discovery of natural product inhibitors of the ubiquitin-proteasome proteolytic signal transduction pathway represents an emerging field. Given these examples, together with the diversity of as yet undiscovered agents, natural product signal transduction agents offer great potential for future drug discovery efforts.
Koehn
Frank E
FE
Natural Products Discovery, Chemical and Screening Sciences, Wyeth Research, 401 North Middletown Road, Pearl River, NY 10965, USA. koehnf@wyeth.com
D001688:Biological Products / Q000627:therapeutic use*; D015195:Drug Design; D020104:Immunophilins / Q000627:therapeutic use*; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D001688:Biological Products; D004364:Pharmaceutical Preparations; D046988:Proteasome Endopeptidase Complex; D020104:Immunophilins