Technologies

Researchers at UC San Diego have developed a small molecule allosteric modulator that is selective for βARs (AS408). The mode of action for this modulator is to act in a positively cooperative manner with inverse agonists, compounds which stabilize the inactive conformation of the receptor. Thus, the positive allosteric modulatory (PAM) effect on inverse agonist and antagonists has significant clinical potential since beta adrenergic antagonists are used in the clinic to treat cardiovascular diseases.

The G protein-coupled receptors (GPCRs) are a very important family of cell surface receptors that respond to extracellular signals which then transduce those signals into intracellular responses. They are also the largest family of targets of currently available therapeutics. Adrenergic receptors belong to the GPCR superfamily and their natural ligands are the catecholamines, epinephrine and norepinephrine. Adrenergic receptors can be further divided into two receptor subfamilies, α and β that exhibit differences in tissue distribution, ligand specificity and cellular output. The β adrenergic receptors (βARs) are important mediators in diseases like asthma, Parkinson’s disease, hypertension and heart failure. Therefore, there is a direct need for new modulators for the βARs receptors.