Chemistry and pharmacology of SMS 201-995, a long-acting octapeptide analogue of somatostatin.
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.
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D004355:Drug Stability; D005934:Glucagon / Q000378:metabolism; D013006:Growth Hormone / Q000378:metabolism; D006168:Guinea Pigs; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D009374:Neoplasms, Experimental / Q000378:metabolism; D015282:Octreotide; D010902:Pituitary Gland / Q000378:metabolism; D011487:Protein Conformation; D051381:Rats; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D017481:Receptors, Somatostatin; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
D007328:Insulin; D017981:Receptors, Neurotransmitter; D017481:Receptors, Somatostatin; D013004:Somatostatin; D013006:Growth Hormone; D005934:Glucagon; D015282:Octreotide