A new peptidic somatostatin agonist with high affinity to all five somatostatin receptors

Eur J Pharmacol. 2002 Dec 5;456(1-3):45-9. doi: 10.1016/s0014-2999(02)02651-1.


All commercially available somatostatin analogs for clinical use have a preference for some but not all somatostatin receptor subtypes. We describe here the synthesis and evaluation in binding and cAMP assays with cell lines stably transfected with sst(1)-sst(5) of a new type of nonapeptide somatostatin analog with a reduced-sized and stabilized structure, Tyr(0)-(cyclo-D-Dab-Arg-Phe-Phe-D-Trp-Lys-Thr-Phe) (KE108). All five somatostatin receptors subtypes have an extremely high affinity for KE108, equivalent to SS-28 at sst(1) and two to four times higher than SS-28 at sst(2), sst(3), sst(4) and sst(5). Moreover, the compound has agonistic properties at all five subtypes, since it is able to inhibit the forskolin-stimulated cAMP production in sst(1)-sst(5) cells. It is stable for several hours in human serum. This analog may therefore represent a considerable improvement over commercially available somatostatin analogs as it will target all somatostatin receptor subtypes, a particular advantage for cancer-related applications, as human cancers can express concomitantly several somatostatin receptor subtypes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding, Competitive
  • CHO Cells
  • Cell Line
  • Colforsin / pharmacology
  • Cricetinae
  • Cyclic AMP / metabolism
  • Dose-Response Relationship, Drug
  • Humans
  • Oligopeptides / chemical synthesis
  • Oligopeptides / metabolism
  • Oligopeptides / pharmacology*
  • Peptides, Cyclic / chemical synthesis
  • Peptides, Cyclic / metabolism
  • Peptides, Cyclic / pharmacology*
  • Protein Isoforms / agonists
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Receptors, Somatostatin / agonists*
  • Receptors, Somatostatin / genetics
  • Receptors, Somatostatin / metabolism
  • Somatostatin / analogs & derivatives
  • Somatostatin / metabolism
  • Somatostatin / pharmacology*
  • Transfection


  • Oligopeptides
  • Peptides, Cyclic
  • Protein Isoforms
  • Receptors, Somatostatin
  • Tyr(0)-(cyclo-D-Dab-Arg-Phe-Phe-D-Trp-Lys-Thr-Phe)
  • Colforsin
  • Somatostatin
  • Cyclic AMP