Chemistry and pharmacology of SMS 201-995, a long-acting octapeptide analogue of somatostatin

Scand J Gastroenterol Suppl. 1986;119:54-64. doi: 10.3109/00365528609087432.

Abstract

Starting from a hypothetical conformation of natural somatostatin and a knowledge of the minimal fragment needed for biological activity, a process of rational design and lead optimization has led to the potent, selective, and long-acting analogue SMS 201-995, (formula: see text) which selectively inhibits growth hormone secretion in several animal species for up to 6 h after subcutaneous application. In the rat, SMS inhibits GH, insulin, and glucagon 70, 3, and 23 times more potently than SRIF, resulting in GH/insulin and GH/glucagon selectivities of 20 and 3, respectively. The compound has been shown to inhibit growth of transplantable insulinomas in hamsters and to label selectively a subset of somatostatin receptors in the rat cortex. A radioactively labelled analogue has been used to visualize somatostatin receptors in a GRF-secreting human tumour. The stability and duration of action of SMS 201-995 after subcutaneous injection enable for the first time extended investigations of the clinical utility of somatostatin in various diseases.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Chemical Phenomena
  • Chemistry
  • Drug Stability
  • Glucagon / metabolism
  • Growth Hormone / metabolism
  • Guinea Pigs
  • Insulin / metabolism
  • Insulin Secretion
  • Neoplasms, Experimental / metabolism
  • Octreotide
  • Pituitary Gland / metabolism
  • Protein Conformation
  • Rats
  • Receptors, Neurotransmitter / metabolism
  • Receptors, Somatostatin
  • Somatostatin / analogs & derivatives*
  • Somatostatin / metabolism
  • Somatostatin / pharmacology

Substances

  • Insulin
  • Receptors, Neurotransmitter
  • Receptors, Somatostatin
  • Somatostatin
  • Growth Hormone
  • Glucagon
  • Octreotide