Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Orphan G-protein-coupled receptors (GPCRs) are cloned proteins with structural characteristics common to the GPCRs but that bind unidentified ligands. Orphan GPCRs have been used as targets to identify novel transmitter molecules. Here we describe the isolation from brain extracts and the characterization of the natural ligand of a particular orphan GPCR (SLC-1) that is sequentially homologous to the somatostatin receptors. We show that the natural ligand of this receptor is the neuropeptide melanin-concentrating hormone (MCH). MCH is a cyclic peptide that regulates a variety of functions in the mammalian brain, in particular feeding behaviour. We demonstrate that nanomolar concentrations of MCH strongly activate SLC-1-related pathways through G(alpha)i and/or G(alpha)q proteins. We have analysed the tissue localization of the MCH receptor and find that it is expressed in several brain regions, in particular those involved in olfactory learning and reinforcement mechanisms, indicating that therapies targeting the MCH receptor should act on the neuronal regulation of food consumption.
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PMID:Molecular characterization of the melanin-concentrating-hormone receptor. 1042 68

Vapreotide [Octastatin, Sanvar, RC 160, BMY 41606] is a somatostatin analogue developed at Tulane University School of Medicine, New Orleans, USA, which holds patent rights for vapreotide. Vapreotide provides a much higher metabolic stability than its parent compound. Vapreotide was licensed to Debiopharm for development in Europe. Vapreotide is usually administered SC although a slow-release IM formulation is also available. Other sustained-release formulations are under development. H3 Pharma plans to sign agreements for all indications in the core markets of North America, Europe and in non-core geographic regions during 2003. H3 Pharma will also seek to obtain registration and early market entry in non-core countries with help from partners. Sanvar Immediate Release (IR) has been submitted for approval within the European Union for the treatment of acute oesophageal variceal bleeding (EVB). Sanvar IR has been awarded orphan drug status in the US for EVB. In July 2003, H3 Pharma received written confirmation from the US FDA that the dossier for Sanvar is fileable for registration in the United States for the treatment of esophageal variceal bleeding (EVB). The Sanvar IR (immediate-release) formulation is expected to enter the US market by late 2004. H3 Pharma expects to file for Latin American registration for this indication in the second half of 2003, with registrations in other regions to follow. Sanvar SR has been submitted for Orphan Drug designation.
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PMID:Vapreotide: BMY 41606, RC 160, Sanvar. 1295 5

In the 1980s, the (111)In-labeled somatostatin analog OctreoScan (Covidien, Hazelwood, MO) was developed for imaging of somatostatin receptor subtype 2 (sst(2)) overexpressing tumors. On the basis of this success, peptide receptor radionuclide therapy (PRRT) was developed using similar somatostatin analogs with different therapeutic radionuclides. Clinical application of PRRT demonstrated impressive results on tumor response, overall survival, and quality of life in patients with gastroenteropancreatic neuroendocrine tumors. The peptides 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), Tyr(3)-octreotate (DOTATATE) and DOTA, Tyr(3)-octreotide (DOTATOC) (brand name Onalta), predominantly targeting sst(2), have been granted Orphan Drug status by the European Medicines Agency and the US Food and Drug Administration for application in PRRT. Besides somatostatin receptor-targeting peptides, multiple other radiopeptide analogs were developed targeting several other receptors overexpressed on various tumors. Some of these peptide analogs, including cholecystokinin, gastrin, gastrin-releasing peptide, arginine-glycine-aspartate (RGD)-peptides, and glucagon-like peptide 1 analogs appeared very promising in preclinical and clinical imaging and PRRT studies. Although the success of PRRT with radiolabeled somatostatin analogs has been established, there is still room for improvement. The therapeutic window of PRRT could be enlarged by the use of new and improved targeting compounds, of which new antagonists with excellent tumor to background ratios are very promising. Furthermore, locoregional administration, improved healthy tissue protection, and combination treatment can be applied to increase the effectiveness of PRRT. Combination treatment might include cocktails of different peptide analogs of different therapeutic radionuclides and of radiolabeled peptides with chemotherapeutic or radiosensitizing agents. This review summarizes results of PRRT and describes clinical and preclinical studies regarding PRRT optimizing strategies.
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PMID:Preclinical and clinical studies of peptide receptor radionuclide therapy. 2035 Jun 30