Guanylate cyclase soluble subunit beta-1 (sGCβ1) (sGCβ1)

Soluble guanylate cyclase (sGC) is a key signal-transduction enzyme and the primary intracellular receptor for nitric oxide (NO) [1, 6]. It exists as a heterodimer composed of an alpha subunit and a beta subunit, with the beta-1 subunit (sGCβ1) being the most physiologically relevant and pharmacologically targeted isoform [12, 16]. The beta-1 subunit contains a prosthetic heme group within its H-NOX domain that binds NO, triggering a conformational change that activates the catalytic domain to synthesize cyclic guanosine monophosphate (cGMP) from GTP [2, 15]. cGMP acts as a second messenger to regulate vascular tone, inhibit platelet aggregation, and suppress smooth muscle cell proliferation [2, 10]. In various cardiovascular and pulmonary diseases, the NO-sGC-cGMP signaling pathway is compromised by oxidative stress or reduced NO bioavailability [11, 20]. Therapeutic agents known as sGC stimulators (e.g., riociguat, vericiguat) and sGC activators (e.g., cinaciguat) target the beta subunit to restore cGMP signaling, providing clinical benefits in conditions such as pulmonary arterial hypertension and heart failure [2, 6, 20]. These drugs interact with the beta subunit's heme-binding domain to either sensitize the enzyme to NO or activate it in a heme-independent manner [1, 3]. Clinical use of these modulators has demonstrated efficacy in improving exercise capacity and reducing the risk of cardiovascular death or hospitalization [2, 6, 24]. However, their use is associated with safety concerns such as systemic hypotension and potential embryo-fetal toxicity [2, 24].

Other names

GUCY1B1GUCY1B3GC-S-beta-1GC-SB3GUC1B3GCS-beta-1GCS-beta-3Soluble guanylate cyclase small subunitGuanylate cyclase 1 soluble subunit beta 1

Soluble guanylate cyclase stimulator, Soluble guanylate cyclase activator