Targeted stimulation of the β2-adrenoceptor for the treatment of type 2 diabetes

We have developed a unique platform for the discovery of novel compounds that can precisely modulate GPCRs to achieve discrete signaling outcomes. This has allowed us to synthesize over 1000 compounds that can activate the b2-adrenoceptor (b2-AR) in novel ways.

Of these, ATR-258 exhibits potent anti-diabetic properties by inducing glucose uptake in skeletal muscle without activating pathways associated with adrenergic side effects.

This preclinical work has been validated with a complete toxicology program and the successful completion of a Phase 1 clinical trial in healthy and diabetic volunteers showing that the compound is safe and displaying indication of efficacy.

In the coming 5-years, we will I) further investigate ATR-258 and other ATR-compounds in vitro to better understand the novel and non-conventional signaling they induce, II) study the positive glucose homeostatic effects in vivo in-depth, and III) evaluate the clinical efficacy of ATR-258 in patients suffering from type 2 diabetes.

This project has the possibility to completely transform the understanding of GPCR signaling and it will allow us to assess the therapeutic value of ´targeted’ b2-AR signaling to develop the next generation of treatments for type 2 diabetes and other metabolic disorders.