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.
Jean Claude Reubi  1 ,  Klaus-Peter Eisenwiener ,  Hans Rink ,  Beatrice Waser ,  Helmut R Mäcke
Affiliations
  • 1. Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, University of Berne, Switzerland. [email protected]
PMID: 12450568 DOI: 10.1016/s0014-2999(02)02651-1
Abstract

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.

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