Novel Melanocortin Receptor Probe Discovery

新型黑皮质素受体探针的发现

• 批准号: 9077902
• 负责人: Carrie Haskell-Luevano
• 金额: $ 37.21万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 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/9077902
• 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; Figs - dietary; G-Protein-Coupled Receptors; 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; Pathway interactions; Pharmaceutical Chemistry; Pro-Opiomelanocortin; Regulation; Reporting; Research; Research Project Grants; Risk Factors; Role; Satiation; Stroke; Tertiary Protein Structure; Therapeutic; Transcript; United States; Weight; base; design; drug discovery; feeding; melanocortin receptor; novel; public health relevance; receptor; receptor binding; therapeutic development; therapeutic target; tool

 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，黑皮质素通路已被明确鉴定为参与饱腹感、肥胖和能量稳态的调节。本研究的目的是表征人黑皮质素-4受体（MC 4 R）N-末端1-26结构域肽激动剂，确定其如何与MC 4 R分子相互作用以作为完全激动剂发挥作用。这些数据将用于产生新的和有效的MC 4 R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研究领域的影响可能会挑战现有的基于黑皮质素受体的治疗剂、基于GPCR的治疗剂的配体设计策略的范例，以及提供探测体重和能量稳态的新工具。