PROGRAMS - Obesity
According to the US Centers for Disease Control and Prevention (CDC), the prevalence of obesity, defined as a Body Mass Index (BMI) of greater than 30 kg/m2, represents a significant health concern for the United States. By this criterion, almost one-third of adults in the US are considered obese and more than two-thirds are overweight. The recently reported rise in obesity among children in the US has alarmed medical professionals. Obesity is fast approaching epidemic proportions in many other developed countries, with more than one billion adults now overweight and at least 300 million of them obese. Obesity increases the risk of other serious diseases and adverse health conditions including hypertension, stroke, type 2 diabetes, sleep apnea and some cancers. Unfortunately, existing therapeutics have achieved only marginal efficacy in terms of weight loss and are accompanied by unacceptable side effects. Taken together, the unmet medical need for new obesity treatments is tremendous.
5-HT2C Agonists for Obesity
The 5-HT2C receptor is a G protein-coupled receptor (GPCR) and one of fourteen serotonin 5-HT receptor subtypes. Direct activation of the 5-HT2C receptor in the central nervous system as a mechanism to reduce food intake is a well validated approach for the treatment of obesity. Preclinical studies using selective 5-HT2C agonists in animal models of obesity, as well as phenotypic and pharmacological characterization of 5-HT2C knock-out mice, have provided evidence that 5-HT2C stimulation is an effective method for promoting weight loss. Furthermore, data generated for 5-HT2C agonists in human clinical studies of anti-obesity treatments have confirmed this therapeutic approach in humans. Our novel indole-based agonists have demonstrated potent 5-HT2C receptor activity, considerable selectivity against other serotonin receptor family members and significant reduction of food intake in industry standard animal models of obesity. Based on this set of highly desirable characteristics, our goal is to generate best-in-class molecules for the safe and effective treatment of obesity.
