Novel Melanocortin Receptor Probe Discovery

新型黑皮质素受体探针的发现

基本信息

批准号：
9449442
负责人：
Carrie Haskell-Luevano
金额：
$ 37.62万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-04-01 至 2020-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9449442
关键词：
ART protein Adverse effects Affect Agonist Amino Acids Area Binding Body mass index Brain Central Nervous System Agents Clinical Trials Complex Country Coupled Data Developed Countries Diet Disease Exercise Fatty acid glycerol esters GTP-Binding Proteins Genes Genetic Goals Heart Diseases Homeostasis Homodimerization Human Hyperphagia Hypertension Knowledge Ligands Link Malignant Neoplasms Mediating Melanocortin 3 Receptor Melanocortin 4 Receptor Modification Molecular Molecular Mechanisms of Action Molecular Probes Morbidity - disease rate Mus N-terminal Neurosecretory Systems Non-Insulin-Dependent Diabetes Mellitus Obesity Outcome POMC gene Pathway interactions Pharmaceutical Chemistry Pharmacology Physiological Pro-Opiomelanocortin Regulation Reporting Research Research Project Grants Risk Factors Role Satiation Stroke Tertiary Protein Structure Therapeutic Transcript United States Weight antagonist G base design drug discovery feeding melanocortin receptor novel public health relevance receptor receptor binding therapeutic development therapeutic target tool

项目摘要

DESCRIPTION (provided by applicant): Obesity afflicts millions of people, and is a major risk factor for Type II diabetes and morbidity. The melanocortin pathway has been clearly identified in mice and humans to be involved in the regulation of satiety, obesity, and energy homeostasis. The goal of this research project is characterize the human melanocortin-4 receptor (MC4R) N- terminal 1-26 domain peptide agonist, identify how it molecularly interacts with the MC4R to mechanistically function as a full agonist. These data will be used to generate novel and potent MC4R agonist molecules as molecular probes and potential central nervous system (CNS) drugs. The impact of the anticipated results on the medicinal chemistry and obesity research fields could challenge the existing paradigms for ligand design strategies for melanocortin receptor based therapeutics, GPCR based therapeutics, as well as provide novel tools to probe weight and energy homeostasis.

描述（由适用提供）：肥胖症遭受了数百万的人，是II型糖尿病和发病率的主要危险因素。在小鼠和人类中清楚地鉴定出了黑色皮质素途径参与饱腹感，肥胖和能量稳态的调节。该研究项目的目标是人类黑素皮质素-4受体（MC4R）N-末端1-26结构域肽激动剂，确定其分子与MC4R如何与MC4R相互作用以机械起作用充当完整的激动剂。这些数据将用于生成新颖和潜在的MC4R激动剂分子作为分子问题和潜在的中枢神经系统（CNS）药物。预期结果对医学化学和肥胖研究领域的影响可能会挑战现有的基于黑素性受体受体治疗，基于GPCR的治疗的配体设计策略的范式，并提供新的工具来探测体重和能量稳态。