Potential clinical indications for a CCK₂ receptor antagonist

Boyce, Malcolm, Lloyd, Katie A ORCID: 0000-0002-2325-8050 and Pritchard, D Mark ORCID: 0000-0001-7971-3561 (2016) Potential clinical indications for a CCK₂ receptor antagonist. CURRENT OPINION IN PHARMACOLOGY, 31. pp. 68-75.

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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 CCK₂ versus CCK₁ receptor, 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.

Item Type:	Article
Uncontrolled Keywords:	Gastric Acid, Animals, Humans, Neuroendocrine Tumors, Stomach Neoplasms, Pancreatic Neoplasms, Disease Models, Animal, Phenylurea Compounds, Benzodiazepinones, Gastrins, Receptor, Cholecystokinin B, Antineoplastic Agents, Drug Design
Depositing User:	Symplectic Admin
Date Deposited:	07 Oct 2016 15:37
Last Modified:	12 Oct 2023 04:43
DOI:	10.1016/j.coph.2016.09.002
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3003679