2. Academic Validation
  3. Synthesis and biological activities of potent peptidomimetics selective for somatostatin receptor subtype 2

Synthesis and biological activities of potent peptidomimetics selective for somatostatin receptor subtype 2

  • Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10836-41. doi: 10.1073/pnas.95.18.10836.
L Yang 1,  S C Berk,  S P Rohrer,  R T Mosley,  L Guo,  D J Underwood,  B H Arison,  E T Birzin,  E C Hayes,  S W Mitra,  R M Parmar,  K Cheng,  T J Wu,  B S Butler,  F Foor,  A Pasternak,  Y Pan,  M Silva,  R M Freidinger,  R G Smith,  K Chapman,  J M Schaeffer,  A A Patchett
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry, Merck Research Laboratories, P.O. Box 2000, Rahway, NJ 07065, USA.
PMID: 9724791 DOI: 10.1073/pnas.95.18.10836
Abstract

A series of nonpeptide somatostatin agonists which bind selectively and with high affinity to Somatostatin Receptor subtype 2 (sst2) have been synthesized. One of these compounds, L-054,522, binds to human sst2 with an apparent dissociation constant of 0.01 nM and at least 3,000-fold selectivity when evaluated against the other somatostatin receptors. L-054,522 is a full agonist based on its inhibition of forskolin-stimulated Adenylate Cyclase activity in Chinese hamster ovary-K1 cells stably expressing sst2. L-054,522 has a potent inhibitory effect on growth hormone release from rat primary pituitary cells and glucagon release from isolated mouse pancreatic islets. Intravenous infusion of L-054,522 to rats at 50 microgram/kg per hr causes a rapid and sustained reduction in growth hormone to basal levels. The high potency and selectivity of L-054, 522 for sst2 will make it a useful tool to further characterize the physiological functions of this receptor subtype.

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