[Multimeric receptors, new targets for the pharmaceutical industry].
Cytokines and growth factors are reported to play a pivotal role in many pathologic conditions. Some recombinant proteins have demonstrated powerful therapeutic activities for example in arthritis for anti-TNF (antibody and soluble receptor) or in cancer for interleukin2 and are now available for clinical use. However limitation in production, treatment condition for use and final high costs have encouraged pharmaceutical industry to develop research of small synthetic compounds which can replace or inhibit natural ligands. During the last 5 years a series of publication have demonstrated that small peptides (up to 20 amino-acids) and non-peptide synthetic compounds may replace in vitro as well as in vivo some cytokine and cell growth factors. Selection of these compounds have used new technique of screening including phage display and gene reporter assays. Currently selected compounds mainly act as agonist and stimulate transduction signals in the target cell as do natural ligands. These results have demonstrated that at least for some cytokine and cell growth factor protein biological action may be mimicked by small molecular weight synthetic compound. Next steps will deal with selection of drug candidates able to be studied at the clinical level.
Dutartre
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Laboratoires Fournier S.A., 50, rue de Dijon, 21121 Daix. p.dutartre@fournier.fr
D000595:Amino Acid Sequence; D016207:Cytokines / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology; D015195:Drug Design; D004345:Drug Industry; D004358:Drug Therapy; D006131:Growth Inhibitors; D006133:Growth Substances / Q000819:agonists / Q000502:physiology; D006801:Humans; D010446:Peptide Fragments; D019151:Peptide Library; D011956:Receptors, Cell Surface; D015398:Signal Transduction
D016207:Cytokines; D006131:Growth Inhibitors; D006133:Growth Substances; D010446:Peptide Fragments; D019151:Peptide Library; D011956:Receptors, Cell Surface
Les récepteurs multimériques, de nouvelles cibles pour l'industrie pharmaceutique.