Rapid Identification of Subtype-Selective Agonists of the Somatostatin Receptor Through Combinatorial Chemistry

• DOI: 10.1126/science.282.5389.737
• Publication Date: 2002-07-27T09:50:14Z
• Authors: Susan P. Rohrer; Elizabeth T. Birzin; Ralph T. Mosley; Scott C. Berk; Steven M. Hutchins; Dong-Ming Shen; Yusheng Xiong; Edward C. Hayes; Rupa M. Parmar; Forrest Foor; Sudha W. Mitra; Sylvia J. Degrado; Min Shu; John M. Klopp; Sheng-Jian Cai; Allan Blake; Wanda W. S. Chan; Alex Pasternak; Lihu Yang; Arthur A. Patchett; Roy G. Smith; Kevin T. Chapman; James M. Schaeffer
• Keywords: Somatostatin receptor 1

Nonpeptide agonists of each the five somatostatin receptors were identified in combinatorial libraries constructed on basis molecular modeling known peptide agonists. In vitro experiments using these selective compounds demonstrated role subtype-2 receptor inhibition glucagon release from mouse pancreatic alpha cells and subtype-5 as a mediator insulin secretion beta cells. Both regulated growth hormone rat anterior pituitary gland. The availability high-affinity, subtype-selective for provides direct approach to defining their physiological functions.