Omran Ziad
College of Pharmacy, Umm AlQura University, Al-Abidiyya, Makkah 21955, Kingdom of Saudi Arabia.
Mini Rev Med Chem. 2017;17(1):51-61. doi: 10.2174/1389557516666160617100328.
Obesity is growing at an alarming rate with huge consequences on health and economy. The worldwide prevalence of obesity has nearly doubled in less than 35 years. Obesity causes many physiological dysfunctions that affect nearly every organ producing multiple morbidities. Despite these facts, there is still no clear, well-defined solution. Notwithstanding the devastating prevalence and consequences of obesity, today only five medicines, orlistat, lorcaserin, phentermine-topiramate, bupropion-naltrexone and liraglutide, are approved by the FDA for long-term treatment of obesity. In this review, the current approaches to treat obesity such as the development of diacylglycerol Oacyltransferase- 1 inhibitors, growth hormone secretagogue receptor-1a antagonists/inverse agonists, melanocortin-3 receptors agonists and melanin concentrating hormone receptor-1 antagonists, will be discussed. The main focus will be on the molecules that were able to reach clinical trials. The last section is dedicated to the "browning" phenomenon of white adipose tissues and the potential of Aldh1a1 inhibitors to treat obesity.
肥胖症正以惊人的速度增长,对健康和经济造成巨大影响。在不到35年的时间里,全球肥胖症患病率几乎翻了一番。肥胖会导致许多生理功能障碍,几乎影响到每个器官,引发多种疾病。尽管如此,目前仍没有明确、确切的解决方案。尽管肥胖症的患病率和后果具有破坏性,但如今美国食品药品监督管理局(FDA)仅批准了五种药物用于肥胖症的长期治疗,即奥利司他、氯卡色林、苯丁胺-托吡酯、安非他酮-纳曲酮和利拉鲁肽。在本综述中,将讨论目前治疗肥胖症的方法,如二酰甘油O-酰基转移酶-1抑制剂、生长激素促分泌素受体-1a拮抗剂/反向激动剂、黑皮质素-3受体激动剂和促黑素聚集激素受体-1拮抗剂的研发情况。主要关注点将是那些能够进入临床试验阶段的分子。最后一部分将专门探讨白色脂肪组织的“褐变”现象以及醛脱氢酶1a1抑制剂治疗肥胖症的潜力。