The inside scoop in GPCRs

Because G protein-coupled receptors are a validated family of targets and play a role in a wide variety of processes such as cellular metabolism and growth, inflammation, neuronal signaling and blood coagulation, there has been an intense effort to determine the function of GPCRs. But the process of going from GPCR gene to drug is difficult, and often does not result in a viable product candidate because of the hydrophobicity of the extracellular domains of many GPCRs.

Indeed, while about half of approved drugs target GPCRs, none do so by interacting with the intracellular surface. Now a study in Nature Medicine has used sequence information to design a peptide that binds to the intracellular region of the protease activated receptor 4 (PAR4) GPCR and has potent anti-thrombotic effects in mice. ...