Melanocortin Selective Ligands

黑皮质素选择性配体

基本信息

批准号：
8243900
负责人：
Carrie Haskell-Luevano
金额：
$ 44.55万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-05-01 至 2016-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8243900
关键词：
ART protein Adverse effects Agonist Anorexia Nervosa Basic Science Biological Blood Pressure Body mass index Brain Bypass Cachexia Complex Country Coupled Data Developed Countries Diet Disease Eating Evaluation Exercise Fatty acid glycerol esters Feeding behaviors Figs - dietary Food Energy Food Intake Regulation G Protein-Coupled Receptor Genes GTP-Binding Proteins Genes Genetic Goals Heart Diseases Homeostasis Human Hyperphagia Hypertension In Vitro Knockout Mice Knowledge Laboratories Lead Ligands Link Malignant Neoplasms Mediating Melanocortin 3 Receptor Melanocortin 4 Receptor Metabolic Modification Morbidity - disease rate Mus Mutagenesis Neuraxis Neurosecretory Systems Non-Insulin-Dependent Diabetes Mellitus Obesity Obesity associated disease Outcome Pathway interactions Peptides Pharmaceutical Chemistry Pharmacology Phenotype Play Pro-Opiomelanocortin Publications Receptor Activation Regulation Research Research Project Grants Risk Factors Role Satiation Stroke Therapeutic Therapeutic Agents Transcript United States Validation Wasting Syndrome Weight base beta-Defensins candidate selection design drug discovery erection feeding human MC4R protein in vivo innovation male melanocortin receptor novel obesity treatment preprohormone receptor research study small molecule tool tumor growth

项目摘要

DESCRIPTION (provided by applicant): 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 drug discovery of MC3R selective molecules (peptide and small molecules), in vitro lead candidate selection, and use of wild type and knockout mice for further molecule lead selection and to probe the role of the MC3R in the novel hypothesis of the MC3R directly involved in the regulation of food intake and satiety. 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.

描述（由申请人提供）：肥胖（体重指数，BMI > 30）困扰着美国和其他国家的数百万人，是心脏病、II 型糖尿病、中风、高血压和其他疾病的主要危险因素。 G 蛋白偶联黑皮质素 3 受体 (MC3R) 在中枢神经系统（大脑）中表达，是参与能量稳态调节的黑皮质素途径的一部分。由于缺乏受体特异性配体以及MC3R敲除小鼠复杂的代谢表型，MC3R在肥胖调节中的具体作用尚未明确。该项目的重点是 MC3R 选择性分子（肽和小分子）的药物发现、体外先导候选物的选择，以及使用野生型和敲除小鼠进行进一步的先导分子选择，并探讨 MC3R 在新假设中的作用MC3R 直接参与食物摄入和饱腹感的调节。预计MC3R配体有潜力成为肥胖相关疾病的治疗配体，绕过人类黑皮质素4受体（MC4R）激动剂相关的男性勃起活动和高血压的副作用。