More than two decades ago, drugmakers searching for new hypertension medications unearthed a mysterious new cell receptor that responded to a hormone known as angiotensin II. This peptide hormone constricts blood vessels, but, oddly, blocking the so-called angiotensin II receptor type 2 (AT2) appeared to have no effect on blood pressure, so the target was largely ignored by drug developers. “Big pharma really just left the AT2 receptor by the side of the road,” says Tom McCarthy, chief executive of Spinifex Pharamceuticals, a company based in Melbourne, Australia, that is exploring the promise of targeting AT2.
Fast forward to today, and scientists now know that AT2 plays a role in everything from tissue repair to inflammation to pain response. A handful of companies are hustling to develop compounds that either block or stimulate this receptor to treat inflammatory diseases, nerve injuries, hypertension and more. In a paper published today, researchers from Spinifex and their collaborators published the first clinical data on a compound that binds to AT2, called EMA401. Results from the placebo-controlled, phase 2 trial suggest that EMA401, which blocks the receptor, can blunt lingering nerve pain due to damage caused by the shingles virus.
AT2 is just one of two receptors known to bind angiotensin II. Several medications that block the other receptor, AT1, have already received market approval for hypertension, diabetic nephropathy and congestive heart failure. When AT2 was first discovered, researchers thought the receptor was “just a little brother,” says Thomas Unger, scientific director of CARIM, Maastricht University’s School for Cardiovascular Diseases in the Netherlands. But Unger and his colleagues now know that AT2 has a “very peculiar and unique combination of effects, which is completely different from the AT1 receptor.”