molecules of the month

A surprisingly safe and possibly efficacious dual-selective αvβ6-αvβ1 inhibitor, providing therapeutic entry to the notoriously challenging TGF-β pathway. Integrins are cell adhesion proteins that help cells bind to the extracellular matrix and have a range of signaling functions. The arginyl-glycinyl-aspartic acid (RGD) subfamily of αv integrins have been studied for decades in a variety of indications including cancer and idiopathic pulmonary fibrosis (IPF). Targeting αv integrins has been attractive yet challenging as they are upstream of transforming growth factor-β (TGF-β), and both small molecule and antibody-based integrin inhibitors have demonstrated preclinical toxicities in non-human primates, including cardiovascular toxicities and hyperplasia. TGF-β is an extensively studied target with established roles across therapeutic areas, but the systemic blockade of its pathway comes…