AdipoAI: An Adiponectin Receptor Agonist for Treatment of Inflammation and Diabetes

BACKGROUND

Adiponectin (APN) is an endogenous protein hormone which binds to Adiponectin Receptors 1 and 2 to exert an anti-inflammatory response and regulate glucose and fatty acid metabolism. Low APN levels in serum are associated with an increased risk of metabolic diseases and inflammatory disorders such as Type 2 Diabetes (T2D), heart disease, periodontitis, and fatty liver disease. Small molecule APN receptor agonists are a  promising class of anti-inflammatory and anti-diabetic therapeutics.

PROBLEM

The size, oral instability, and scalability of adiponectin makes it unattractive as a therapeutic which is why synthetic small molecules such as AdipoRON have been developed. Currently, there is no approved adiponectin agonist due to clinical concerns surrounding the low binding affinity of AdipoRON and off-target effects.

SOLUTION

Dr. Jake Chen’s lab at Tufts University has discovered a novel small molecule APN agonist, AdipoAI, which has been shown to improve the glucose metabolism and ameliorate systemic inflammation in an obesity related (DIO) T2 diabetic  mouse model.

The inventors have demonstrated that AdipoAI:

• Led to a healthy decrease in body weight and improved blood glucose regulation in DIO mice (Fig. 1,2)
• Is more effective than AdipoRON for preventing diabetes-associated dental bone loss and inflammation at lower doses (Fig. 3)
• Attenuates systemic inflammation in diabetic and LPS- induced endotoxemia mice
• Activates adiponectin metabolism related gene expression 

IP STATUS: Issued Patent: US11655212B2 (05/23)

PUBLICATION: A novel adiponectin receptor agonist (AdipoAI) ameliorates type 2 diabetes-associated periodontitis by enhancing autophagy in osteoclasts