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：
9235279
负责人：
Carrie Haskell-Luevano
金额：
$ 37.39万
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/9235279
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 G-substrate 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（由申请人提供）：肥胖困扰着数百万人，是 II 型糖尿病和发病的主要危险因素。在小鼠和人类中已明确发现黑皮质素途径参与饱腹感、肥胖和能量的调节。该研究项目的目标是表征人类黑皮质素 4 受体 (MC4R) N 末端 1-26 结构域肽激动剂，并确定其分子机制。与 MC4R 相互作用，以机械方式发挥完全激动剂的作用。这些数据将用于生成新型有效的 MC4R 激动剂分子，作为分子探针和潜在的中枢神经系统 (CNS) 药物。预期结果对药物化学和肥胖的影响。研究领域可以挑战基于黑皮质素受体的治疗、基于 GPCR 的治疗的配体设计策略的现有范式，并提供探测体重和能量稳态的新工具。