Novel THC/Anandamide Hybrids as Appetite Suppressants

新型 THC/Anandamide 混合物作为食欲抑制剂

• 批准号: 7121505
• 负责人: Anuradha Mahadevan
• 金额: $ 24.44万
• 依托单位: ORGANIX, INC.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-15 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7121505
• 关键词: analog; anandamide; anorexic agent; appetite; cannabinoid receptor; drug design /synthesis /production; inhibitor /antagonist; laboratory mouse; obesity

Obesity has reached epidemic proportions and in a year about 300,000 people die of obesity-related diseases. Annual medical spending due to obesity and overweight is about $117 billion. There is an urgent need to discover effective drugs to treat this disease since existing drugs have modest efficacy and significant side effects. A potentially promising target for anti-obesity drugs is the cannabinoid (CB1) receptor. In Phase I of this proposal our focus will be on the structural optimization of our novel THC/anandamide template to discover one or more CB1 receptor antagonists. In order to distinguish between agonist and antagonist activity, analogs that bind effectively to the CB1 receptor, will be evaluated for their ability to stimulate [35S]GTPgS binding. Our specific objective is to discover and select the best analogs in this series that manifest in vivo activity in a mouse model for appetite suppression. If the above objective is accomplished in Phase I, we will have a drug candidate for further development in Phase II. The long-term objective of this proposal is to develop a novel anti-obesity drug that is both safe and effective.

肥胖已达到流行病的程度，一年内约有 30 万人死于与肥胖相关的疾病。因肥胖和超重导致的年度医疗支出约为 1170 亿美元。由于现有药物疗效有限且副作用显着，迫切需要发现治疗该疾病的有效药物。抗肥胖药物的一个潜在有前景的靶点是大麻素（CB1）受体。在该提案的第一阶段，我们的重点将是我们的新型 THC/anandamide 模板的结构优化，以发现一种或多种 CB1 受体拮抗剂。为了区分激动剂和拮抗剂活性，将评估有效结合CB1受体的类似物刺激[35S]GTPgS结合的能力。我们的具体目标是发现并选择该系列中最好的类似物，这些类似物在小鼠模型中表现出体内食欲抑制活性。如果以上情况 第一阶段的目标已经实现，我们将在第二阶段有进一步开发的候选药物。该提案的长期目标是开发一种安全有效的新型抗肥胖药物。