Kowalski Timothy J, McBriar Mark D
Department of Cardiovascular/Metabolic Disease Research, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
Expert Opin Investig Drugs. 2004 Sep;13(9):1113-22. doi: 10.1517/13543784.13.9.1113.
The compelling genetic and pharmacological evidence implicating melanin-concentrating hormone-1 receptor (MCH-1R) signalling in the regulation of food intake and energy expenditure has generated a great deal of interest by pharmaceutical companies for the discovery of MCH-1R antagonists, evidenced by the increased number of patents describing MCH-1R antagonists for the treatment of obesity and metabolic syndrome. The structural diversity of small molecular weight drug-like MCH-1R antagonists produced and preclinical studies showing hypophagia and weight loss with small molecular weight and peptidal antagonists in rodents is encouraging and suggests that the identification of clinical candidates will be forthcoming.
有力的遗传学和药理学证据表明,黑色素浓缩激素-1受体(MCH-1R)信号传导参与食物摄入和能量消耗的调节,这引起了制药公司对发现MCH-1R拮抗剂的极大兴趣,描述用于治疗肥胖症和代谢综合征的MCH-1R拮抗剂的专利数量增加就证明了这一点。所生产的小分子量类药物MCH-1R拮抗剂的结构多样性以及临床前研究表明,啮齿动物使用小分子和肽类拮抗剂后出现摄食减少和体重减轻,这令人鼓舞,并表明即将确定临床候选药物。