It’s the water! The open and shut case of drug-induced integrin activation

Integrin receptors are established drug targets, but many of the drugs that have been developed act as partial agonists, inducing the receptor into a high-affinity, ligand-binding state. Lin et al. discovered a general mechanism to circumvent this problem—stabilizing a key water molecule that prevents receptor activation. Their findings are likely to impact future therapeutic development. Integrin receptors are established drug targets, but many of the drugs that have been developed act as partial agonists, inducing the receptor into a high-affinity, ligand-binding state. Lin et al. discovered a general mechanism to circumvent this problem—stabilizing a key water molecule that prevents receptor activation. Their findings are likely to impact future therapeutic development.