CGP42112: the full AT(2) receptor agonist and its role in the renin–angiotensin–aldosterone system: no longer misunderstood

For years, the AT(2)R-selective ligand CGP42112 has been erroneously characterized as a partial agonist, partly due to its ability to also interact with the AT(1)R at high concentrations. As late as 2009, it was still being characterized as an antagonist as well. In this perspective/opinion piece, we try to resolve the ambiguity that surrounds the efficacy of this compound by extensively reviewing the literature, tracing its beginnings to 1989, showing that CGP42112 has never been convincingly shown to be a partial agonist or an antagonist at the AT(2)R. While CGP42112 is now routinely characterized as an AT(2)R agonist, regrettably, there is a paucity of studies that can validate its efficacy as a full agonist at the AT(2)R, leaving the door open for continuing speculation regarding the extent of its efficacy. Hopefully, the information presented in this perspective/opinion piece will firmly establish CGP42112 as a full agonist at the AT(2)R such that it can once again be used as a tool to study the AT(2)R.