Relaxin family peptide receptor 1 (RXFP1) (RXFP1)

The Relaxin family peptide receptor 1 (RXFP1), also known as LGR7, is a Class A G protein-coupled receptor that serves as the primary physiological mediator for the hormone relaxin-2. It is structurally unique among GPCRs, featuring a large extracellular domain with ten leucine-rich repeats and an N-terminal low-density lipoprotein class A (LDLa) module that is essential for receptor activation and signaling. Activation of RXFP1 triggers a pleiotropic intracellular cascade involving cAMP, nitric oxide (NO), and PI3K/Akt pathways, which collectively promote vasodilation, inhibit myofibroblast activation, and stimulate the degradation of extracellular matrix components. Due to its potent anti-fibrotic and cardiovascular protective effects, RXFP1 is a major therapeutic target for acute and chronic heart failure, as well as fibrotic disorders of the lung, kidney, and liver. While the recombinant human relaxin-2 analog serelaxin demonstrated significant survival benefits in early trials, it failed to meet primary endpoints in Phase III studies (RELAX-AHF-2), leading to a shift in drug development toward long-acting analogs like AZD3427 and TX45, as well as small-molecule allosteric agonists like ML290. Clinical challenges in targeting this pathway include the extremely short half-life of native relaxin and the potential for dose-limiting hypotension.

Other names

Leucine-rich repeat-containing G-protein-coupled receptor 7LGR7Relaxin receptor 1RXFPR1Great cysteine-rich protein 7

Agonism (activation of the receptor leads to increased cAMP production, nitric oxide (NO) signaling, and activation of the PI3K/Akt and ERK1/2 pathways)