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Adenylyl cyclase activators and inhibitors act on the enzymes that make a central second messenger. Each catalytic cycle turns adenosine triphosphate (ATP) into cyclic adenosine monophosphate (cAMP) and releases pyrophosphate. Mammals have nine membrane-bound isoforms (AC1 to AC9), regulated by G proteins, and one soluble adenylyl cyclase (sAC). Forskolin, a plant diterpene, was shown in 1981 to activate the enzyme directly, and NKH477 is a water-soluble derivative. The soluble enzyme, described as a cytosolic form in 1999, responds to bicarbonate and calcium rather than to G proteins. LRE1, reported in 2016 as an allosteric inhibitor, and KH7 both block sAC selectively. ST034307 is listed as an AC1 inhibitor, and 2',5'-dideoxyadenosine acts as a broad P-site inhibitor.
VHC-7 is a selective agonist of adenylyl cyclase type 8 (AC8), exhibiting an EC50 value of 105.2 nM. This compound effectively elevates levels of cyclic adenosine monophosphate (cAMP), making it a valuable tool for investigating the molecular pathways involved in central nervous system disorders and cardiac diseases. Its targeted mechanism enables detailed studies into the role of AC8 in various physiological and pathological processes.
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Adenylyl cyclase type 2 agonist-1 is a potent agonist of adenylyl cyclase type 2 (AC2) with an EC50 value of 90 nM. This compound has been shown to inhibit the expression of Interleukin-6, suggesting its potential utility in the treatment of respiratory diseases. Its mechanism of action and biological activity make it a valuable tool for research focused on inflammation and related therapeutic areas.
