Self-made allostery: endogenous COMP antagonizes pathologic AT1 A R signaling

The identification and development of biased modulators of proximal G protein-coupled receptor (GPCR) signaling to prevent pathological disease progression has been at the forefront of recent drug discovery efforts. Recently, Fu et al. identified cartilage oligomeric matrix protein (COMP) as an endogenous negative allosteric modulator of beta-arrestin (beta arr)-dependent angiotensin II (Ang II) Type 1A receptor (AT1(A)R) signaling, which attenuates the development of abdominal aortic aneurysm (AAA), a chronic inflammatory vascular disease lacking pharmacological treatment options.