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

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.