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

• Published in: Scandinavian journal of gastroenterology. Supplement Vol. 119; p. 54
• Main Authors: Pless, J, Bauer, W, Briner, U, Doepfner, W, Marbach, P, Maurer, R, Petcher, T J, Reubi, J C, Vonderscher, J
• Format: Journal Article
• Language: English
• Published: England 1986
• Subjects: 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
• ISSN: 0085-5928
• DOI: 10.3109/00365528609087432

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.