Soluble guanylyl cyclase subunit beta-1 (GUCY1B1) (sGC β1)

Soluble guanylyl cyclase (sGC) is a heterodimeric enzyme and the primary intracellular receptor for nitric oxide (NO) (UniProt P33402). It consists of an alpha subunit (α1 or α2) and a beta-1 (β1) subunit, the latter of which contains a prosthetic heme group required for NO binding (Sandner et al., 2021, PMID: 33441155). Upon activation by NO, sGC catalyzes the conversion of GTP to cyclic guanosine monophosphate (cGMP), a key second messenger that regulates vascular tone, platelet activity, and cardiac remodeling (Follmann et al., 2013, PMID: 23863631). Dysregulation of this pathway, often due to oxidative stress or reduced NO bioavailability, is a major driver of cardiovascular diseases such as pulmonary arterial hypertension and heart failure (FDA Label for Verquvo). Pharmacological agents like sGC stimulators and activators target the β1 subunit complex to restore cGMP signaling, offering a therapeutic approach that is independent of or synergistic with endogenous NO.

Other names

GUCY1B3Guanylate cyclase soluble subunit beta-1GC-S-beta-1GCS-beta-1GUCB1Soluble guanylate cyclase small subunit

Drugs targeting the sGC β1 subunit function as either stimulators or activators. sGC stimulators, such as riociguat and vericiguat, stabilize the NO-sGC binding and can also directly stimulate the enzyme in an NO-independent but heme-dependent manner (Sandner et al., 2021, PMID: 33441155). In contrast, sGC activators like cinaciguat target the oxidized (Fe3+) or heme-free form of the enzyme, which is otherwise unresponsive to NO, thereby restoring catalytic activity under conditions of high oxidative stress (Follmann et al., 2013, PMID: 23863631).