title: Potential clinical indications for a CCK2receptor antagonist.
abstract: Gastrin controls gastric acid secretion and mucosal cell growth, especially of enterochromaffin-like cells, via gastrin/cholecystokinin-2 receptor (CCK2R) binding and downstream signalling. Studies in animal models, healthy subjects and patients with gastric neuroendocrine tumours provide compelling evidence to justify developing a CCK2R antagonist (CCK2RA) for preventing or treating the trophic effects of hypergastrinaemia or conditions expressing CCK2R, and with or without a proton pump inhibitor, for treating gastric acid-related conditions. Many compounds have been studied, but most have had problems with potency, selectivity for CCK2versus CCK1receptor, solubility or oral bioavailability. None has yet been marketed. Netazepide and Z-360 are currently undergoing clinical development, for treatment of gastric neuroendocrine tumours and pancreatic cancer, respectively. There are several other potential indications for a CCK2RA and an unmet need.
authors.affiliation: Hammersmith Medicines Research (HMR), Cumberland Avenue, London NW10 7EW, UK.
authors.forename: Malcolm
authors.initials: M
authors.lastname: Boyce
authors.affiliation: Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Crown Street, Liverpool L69 3GE, UK.
authors.forename: Katie A
authors.initials: KA
authors.lastname: Lloyd
authors.affiliation: Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Crown Street, Liverpool L69 3GE, UK. Electronic address: Mark.pritchard@liv.ac.uk.
authors.forename: D Mark
authors.initials: DM
authors.lastname: Pritchard
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001570:Benzodiazepinones / Q000494:pharmacology; D004195:Disease Models, Animal; D015195:Drug Design; D005744:Gastric Acid / Q000378:metabolism; D005755:Gastrins / Q000378:metabolism; D006801:Humans; D018358:Neuroendocrine Tumors / Q000188:drug therapy / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000473:pathology; D010671:Phenylurea Compounds / Q000494:pharmacology; D043887:Receptor, Cholecystokinin B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D001570:Benzodiazepinones; D005755:Gastrins; D010671:Phenylurea Compounds; D043887:Receptor, Cholecystokinin B; C528831:Z-360; C104428:YF 476