G protein-coupled receptors are the most prolific initiators of cell signaling pathways. The largest class of drug targets, they are also, unfortunately, the most intractable to drug development. Three research papers shows how combining different techniques -- crystallography, hydrogen exchange, and electron microscopy -- can shed new light on the nuances of GPCR signaling and how this kind of integrated approach could help identify new drug targets.

Roche’s decision to discontinue a Phase III program in idiopathic pulmonary fibrosis was the latest of several recent late-stage clinical failures, emblematic of the difficulty in finding new approaches to treat the disease.