Selectivity somatostatin receptor subtypes

Martin, R.F., Green, L.G., Guba, W., Kratochwil, N., and Christ, A. (2007) Discovery of the first nonpeptidic, small-molecule, highly selective somatostatin receptor subtype 5 antagonists a chemogenomics approach. Journal of Medicinal Chemistry, 50, 6291-6294. 

Law SF, Yasuda K, Bell GI, Reisine T. Gia3 and Goa selectively associate with the cloned somatostatin receptor subtype... 

Berk, S.C., Rohree, S.P., Degrado, S.J., Birzin, E.T., Mosley, R.T., Hutchins, S.M., Pasternak, A., Schaeffer, J.M., and Underwood, D.J. A combinatorial approach toward the discovery of non-peptide, subtype-selective somatostatin receptor ligands. /. Comb. Chem. 1999, 1, 388-396. 

Figure 2.18 The tetradecapeptide somatostatin is a nanomolar-to-subnanomolar ligand of five different somatostatin receptor subtypes. Compounds 62-66 are structurally simplified analogs from four combinatorial libraries, with up to 350 000 members per library. Each compound shows a remarkable selectivity against the different sstl-sst5 receptor subtypes (Table 2.1). The orientation of the compounds follows a projection of their superposition with a Merck cyclopeptide.

Veber et al. (31) This approach yielded five compounds (73-77) (Fig. 15.33), each being selective for one of the somatostatin receptor subtypes sstl (73), sst2 (74), sst3 (76), sst4 (76), and sst5 (77). 

Other more recent examples of new receptor subtypes include neurokinin, melanocortin and somatostatin receptor subtypes. Neurokinins (substance P, neurokinin A and neurokinin B) act at three receptor subtypes NKj, NKj and NK,. Selective ligands are being explored for the treatment of pain, asthma, depression, etc. The natural melanocortic peptides are derived from the precursor peptide pro-opiomelanocortin... 

REUBI, J.C., et al., Affinity profiles for human somatostatin receptors subtypes SST1-SST5 of somatostatin radiotracers selected for scintigraphic and radio-therapeutic use, Eur. J. Nucl. Med. 27 (2000) 273-282. 

Law SF, Zaina S, Sweet R, Yasuda K, Bell GI, Stadel J, Reisine T (1994) Gi alpha 1 selectively couples somatostatin receptor subtype 3 to adenyl cyclase identification of the functional domains of this alpha subunit necessary for mediating the inhibition by somatostatin of cAMP formation. Mol Pharmacol 45 587-590 Leroux P, Querion R, Pelletier G (1985) Localization and characterization of brain somatostatin receptors as studied with somatostatin-14 and somatostatin-28 receptor radioautography. Brain Res 347 74-84... 

Liapakis G, Tallent M, Reisine T (1996c) Molecular and functional properties of somatostatin receptor subtypes. Metabolism 1 12-13 Libert F, Parmentier M, Lefort A, Dinsart C, Wan Sande J, Maenhaut C, Simons M-J, DuMont JE, Vassart G (1989) Selective amplification and cloning of four new members of the G protein-coupled receptor family. Science 244 569-572 Liu YF, Jakobs KH, Rasenick MM, Albert PR (1994) G protein specificity in receptor-effector coupling. Analysis of the roles of Go and Giz in GH4C1 pituitary cells. J Biol Chem 269 13880-13886... 

S.P. Rohrer, J.M. Schaeffer, Identification and characterization of subtype selective somatostatin receptor agonists, J. Physiol. 2000, 94, 211-215. 

Chemical genetic screens have identified several small molecules targeting a TGF- i-responsive reporter gene, arresting mammalian cells in mitosis, uihibiting the function of tumor suppressor p53, and acting as subtype-selective somatostatin receptor agonist. 

Rohrer SP, Birzin ET, Mosley RT, et al. Rapid identification of subtype-selective agonists of the somatostatin receptor through combinatorial chemistry. Science 1998 282 737- 0. 

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