{'fraction_non_alphanumeric': 0.01838235294117647, 'fraction_numerical': 0.009978991596638655, 'mean_word_length': 5.414141414141414, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 1, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Development of somatostatin receptor subtype selective agonists through combinatorial chemistry.

Non-peptide agonists of each of the five somatostatin receptors were identified from a combinatorial mixture library and three follow-up libraries. The initial library (20 x 20 x 79) was patterned after a lead structure which was identified by screening a set of molecules selected on the basis of molecular modeling of known peptide agonists of the somatostatin subtype-2 receptor (SSTR2). A second library with increased complexity (21 x 22 x 147) was designed around the same lead structure. Third and fourth libraries of aryl-indole compounds were designed, based on information that had been obtained by screening the first two libraries in five somatostatin receptor ligand-binding assays. Actives were chosen based on potency and receptor subtype selectivity profiles. The identity of each subtype selective compound present in active mixtures was determined by an iterative deconvolution process using resins archived from each step of the original synthesis. The approach of complex mixture screening was well validated with each of the five somatostatin receptors. The advantages of mixture screening with respect to manpower requirements, reagent consumption, and time to identify an active pure compound from a mixture were well illustrated in the course of this work. The availability of these high affinity, subtype selective agonists for each of the somatostatin receptors provided a direct approach to defining their physiological functions. In vitro experiments demonstrated the role of the somatostatin subtype-2 receptor (SSTR2) in inhibition of glucagon release from mouse pancreatic a-cells and the somatostatin subtype-5 receptor (SSTR5) as a mediator of insulin secretion from pancreatic b-cells. Both receptors regulated growth hormone release from the rat anterior pituitary gland.