Small organic ligands for the ecdysone receptor – agrochemicals, gene switches, and beyond

While pesticides are essential for the world to meet its increasing demand for food, off-target toxicity in humans and other species is an ongoing environmental issue. There is a strong motivation for developing more selective pesticides that can target pest insects, for example, while being benign for beneficial insects such as bees, and other nontarget species more generally. The ecdysone receptor is absent in vertebrates so constitutes a very useful target for green insecticides. It has also been found to be an extremely useful gene switch in molecular biology. While the natural ecdysone ligands are complex steroidal compounds, a wide range of simpler synthetic agonists and antagonists have been developed. Here we review the diversity of chemotypes that have been shown to bind productively to the ecdysone receptor and have found application as insecticides and gene switches. We discuss the similarities and differences in these chemotypes, the origin of which is the remarkable flexibility of the ligand binding domain in the receptor. We provide a perspective on the discovery of further useful chemotypes with potentially higher binding and selectivity between pest and beneficial insects.<p></p>