A guanylate cyclase activator (or "GUCA") is a member of a group of proteins that upregulate guanylate cyclase. GUCA is also known as guanylate cyclase-activating protein (or "GCAP"). Its mutations can be associated with vision defects. [1]
There are five genes involved:
There are several therapeutic drugs that act as GUCAs, including linaclotide and plecanatide, which are guanylate cyclase-C receptor agonists. These drugs increase the secretion of bicarbonate and chloride in the colon and potentially relieve visceral hypersensitivity in IBS-C patients. [2]
Guanyl cyclase targeting drug, Cinaciguat has emerged in recent years as one of the first in the class of soluble guanyl cyclase activator. Soluble guanyl class is a version of guanyl cyclase that has a primary preference for nitric oxide(NO) sensitivity, with some variants beings more insensitive to NO than others but still remaining soluble within the cell cytosol. [3] Cinaciguat targets the specifically the soluble form of guanyl cyclase. This guanyl that triggers reduced blood flow through GTP to cGMP conversion. The cGMP acts as a secondary messenger to target reduced blood flow pathways. This pathway has been linked to several cardiovascular diseases, such as ADHF(acute decompensated heart failure) which Cinaciguat has been developed to target. [4]