Melanocortin Receptor Selective Ligands

肥胖(BMI&GT；30)困扰着美国数百万人， 其他国家，是心脏病、II型糖尿病、 中风、高血压和发病率。G蛋白偶联的黑素皮质素-3受体 (MC3R)在中枢神经系统(脑)中表达，是 黑素皮质素途径参与能量稳态的调节。具体的角色 由于缺乏对MC3R在肥胖调控中的作用的明确定义 受体特异性配体与MC3R基因敲除的复杂代谢表型 老鼠。本项目的重点是发现MC3R选择性分子探针。 (多肽和小分子)，体外领先候选选择，以及野生型和 基因敲除小鼠进行进一步的分子铅选择。该项目的工作假设 MC3R直接参与调节食物摄入量、饱腹感和 能量/代谢动态平衡。预计MC3R配体具有潜在的 成为绕过人类的肥胖相关疾病的治疗配体 黑素皮质素-4受体激动剂与男性勃起活动的副作用相关 还有高血压。

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.