Inward rectifier potassium (Kir) channels play critically important roles in diverse tissues and organs and might represent novel drug targets for a variety of human diseases. The lack of small-molecule probes for specific Kir channels has hampered efforts to explore the therapeutic potential of most Kir channel family members. A major focus of our group is to develop potent, specific, and in vivo-active small-molecule tool compounds for evaluating Kir channel integrative physiology and therapeutic potential. The figure below shows the Kir2.2 channel crystal structure with small-molecule binding sites identified in other Kir channels highlighted with spheres. Reviewed in Swale et al., Current Opinion in Pharmacology, 2014.