Adventures in Glutamate: The Difficult and Expensive Path of Novelty in Drug Discovery

The discovery of metabotropic glutamate receptors in the early '90s opened up a new world of potential drug targets in CNS diseases and beyond. But targeting specific mGluRs proved difficult; eventually the challenge of designing selective molecules led to breakthroughs modulating receptors at sites distinct from the endogenous binding site. This so-called allosteric modulation may help to clear a logjam of undruggable GPCRs and other receptors. Creating drug-like molecules remains a challenge but industry, after some false starts, is poised to make advances as compounds begin to hit proof-of-concept in man.