Melanocortin Receptor Selective Ligands

黑皮质素受体选择性配体

• 批准号: 10557972
• 负责人: Marc Giulianotti
• 金额: $ 11.15万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10557972
• 关键词: ART protein; Acute; Age; Agonist; Basic Science; Biological; Blood Pressure; Body mass index; Brain; Bypass; Collection; Complex; Country; Coupled; Data; Developed Countries; Diet; Disease; Eating; Energy Intake; Energy Metabolism; Exercise; Fatty acid glycerol esters; Feeding behaviors; Food Energy; Food Intake Regulation; G-Protein-Coupled Receptors; GTP-Binding Proteins; Genes; Genetic; Goals; Heart Diseases; Homeostasis; Human; Hyperphagia; Hypertension; Hypothalamic structure; In Vitro; Knockout Mice; Lead; Ligands; Mediating; Melanocortin 3 Receptor; Melanocortin 4 Receptor; Metabolic; Modification; Molecular Probes; Morbidity - disease rate; Mus; Neuraxis; Neurons; Neurosecretory Systems; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Obesity associated disease; Outcome; POMC gene; Pathway interactions; Peer Review; Peptides; Persons; Pharmaceutical Chemistry; Phenotype; Physiological; Physiology; Play; Population; Pro-Opiomelanocortin; Publications; Receptor Activation; Regulation; Reporting; Research; Research Project Grants; Risk Factors; Role; Satiation; Stroke; Therapeutic; Therapeutic Agents; Transcript; United States; Validation; Weight; antagonist; antagonist G; base; blood glucose regulation; candidate selection; design; drug discovery; erection; experimental study; genetic manipulation; in vivo; in vivo evaluation; lead candidate; male; melanocortin receptor; metabolic phenotype; mouse genetics; obesity treatment; preprohormone; rational design; receptor; screening; side effect; small molecule; small molecule libraries; tool

Obesity (body mass index, BMI >30) afflicts millions of people in the United States and other countries, and is a major risk factor for heart disease, type II diabetes mellitus, stroke, hypertension, and morbidity. The G-protein coupled melanocortin-3 receptor (MC3R) is expressed in the central nervous system (brain) and is part of the melanocortin pathway involved in the regulation of energy homeostasis. The specific role of the MC3R in the regulation of obesity has not been clearly defined due to a lack of receptor specific ligands and a complex metabolic phenotype of the MC3R knockout mouse. This project is focused upon the discovery of MC3R selective molecular probes (peptide and small molecules), in vitro lead candidate selection, and use of wild type and knockout mice for further molecule lead selection. The working hypothesis of this project is that the MC3R is directly involved in the regulation of food intake, satiety, and energy/metabolic homeostasis. It is anticipated that MC3R ligands have the potential to become therapeutic ligands for obesity related diseases that bypass the human melanocortin-4 receptor (MC4R) agonist associated side effects of male erectile activity and hypertension.

在美国和欧洲，数以百万计的人饱受肥胖（身体质量指数，BMI）的折磨