ArticleBritish journal of pharmacology2016
Pharmacological characterization of the first in class clinical candidate PF-05190457: a selective ghrelin receptor competitive antagonist with inverse agonism that increases vagal afferent firing and glucose-dependent insulin secretion ex vivo.
Article in British journal of pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 26 citations in OpenAlex.
- Pharmacokinetic and pharmacodynamic results from a randomized controlled study with the growth hormone secretagogue receptor blocker PF-5190457 in recently abstinent patients with alcohol use disorder.The international journal of neuropsychopharmacology · 2026Trial
- A randomized, double-blind, placebo-controlled study of a GHSR blocker in people with alcohol use disorder.JCI insight · 2024Trial
- Pharmacokinetics and pharmacodynamics of PF-05190457: The first oral ghrelin receptor inverse agonist to be profiled in healthy subjects.British journal of clinical pharmacology · 2017Trial
- Peptide Hormones in Appetite Regulation: A Complex Network.Pharmaceuticals (Basel, Switzerland) · 2026Review
- The Ghrelin-LEAP2 System in Obesity and Diabetes: Pathophysiological Roles and Therapeutic Potential.Current obesity reports · 2026Review
- An Emerging Role for Gut-Brain Signaling Involving Ghrelin in Chronic Stress.Advances in experimental medicine and biology · 2025Review
- Initial Pharmacological Characterization of a Major Hydroxy Metabolite of PF-5190457: Inverse Agonist Activity of PF-6870961 at the Ghrelin Receptor.The Journal of pharmacology and experimental therapeutics · 2023Article
- The controversial role of the vagus nerve in mediating ghrelin's actions: gut feelings and beyond.IBRO neuroscience reports · 2022Review
- "Sibling" battle or harmony: crosstalk between nesfatin-1 and ghrelin.Cellular and molecular life sciences : CMLS · 2022Review
- Review
- Molecular mechanism of agonism and inverse agonism in ghrelin receptor.Nature communications · 2022Article
- A Population Pharmacokinetic Analysis of PF-5190457, a Novel Ghrelin Receptor Inverse Agonist in Healthy Volunteers and in Heavy Alcohol Drinkers.Clinical pharmacokinetics · 2021Article
- Endocrine effects of the novel ghrelin receptor inverse agonist PF-5190457: Results from a placebo-controlled human laboratory alcohol co-administration study in heavy drinkers.Neuropharmacology · 2020Article
- Interactions Between Alcohol and the Endocannabinoid System.Alcoholism, clinical and experimental research · 2020Review
- The novel ghrelin receptor inverse agonist PF-5190457 administered with alcohol: preclinical safety experiments and a phase 1b human laboratory study.Molecular psychiatry · 2020Article
- Development and validation of an assay for a novel ghrelin receptor inverse agonist PF-5190457 and its major hydroxy metabolite (PF-6870961) by LC-MS/MS in human plasma.Journal of chromatography. B, Analytical technologies in the biomedical and life sciences · 2019Article
- Pharmacological Modulation of Ghrelin to Induce Weight Loss: Successes and Challenges.Current diabetes reports · 2019Review
- Targeting Peripheral CBCell metabolism · 2019Article
- Ghrelin's Relationship to Blood Glucose.Endocrinology · 2019Review
- Ghrelin regulation of glucose metabolism.Peptides · 2018Review
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeGhrelin increases growth hormone secretion, gastric acid secretion, gastric motility and hunger but decreases glucose-dependent insulin secretion and insulin sensitivity in humans. Antagonizing the ghrelin receptor has potential as a therapeutic approach in the treatment of obesity and type 2 diabetes. Therefore, the aim was to pharmacologically characterize the novel small-molecule antagonist PF-05190457 and assess translational pharmacology ex vivo. EXPERIMENTAL APPROACH: Radioligand binding in filter and scintillation proximity assay formats were used to evaluate affinity, and europium-labelled GTP to assess functional activity. Rat vagal afferent firing and calcium imaging in dispersed islets were used as native tissues underlying food intake and insulin secretion respectively. KEY
resultsPF-05190457 was a potent and selective inverse agonist on constitutively active ghrelin receptors and acted as a competitive antagonist of ghrelin action, with a human Kd of 3 nM requiring 4 h to achieve equilibrium. Potency of PF-05190457 was similar across different species. PF-05190457 increased intracellular calcium within dispersed islets and increased vagal afferent firing in a concentration-dependent manner with similar potency but was threefold less potent as compared with the in vitro Ki in recombinant overexpressing cells. The effect of PF-05190457 on rodent islets was comparable with glibenclamide, but glucose-dependent and additive with the insulin secretagogue glucagon-like peptide-1. CONCLUSIONS AND IMPLICATIONS: Together, these data provide the pharmacological in vitro and ex vivo characterization of the first ghrelin receptor inverse agonist, which has advanced into clinical trials to evaluate the therapeutic potential of blocking ghrelin receptors in obesity and type 2 diabetes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.