PC5/6 Inhibitors

Chemical inhibitors of PC5/6 include a range of molecules that target the proteolytic activity of this enzyme through various mechanisms. Decanoyl-RVKR-CMK, a potent irreversible inhibitor, operates by binding covalently to the active site of furin-like convertases, thus reducing the activation of proteins that PC5/6 would typically process. This overlap in substrate specificity between furin and PC5/6 allows the inhibitor to functionally impede PC5/6 activity. Similarly, Hexa-D-arginine acts as a competitive inhibitor by occupying the enzyme's active site with its peptide mimetic structure, preventing PC5/6 from cleaving its natural substrates. Naphthofluorescein also exploits the catalytic similarities between furin and PC5/6, selectively binding to its active site and impeding substrate processing.

In addition to these, α1-Antitrypsin Portland leverages its serpin structure to target furin and by extension can inhibit PC5/6 due to the structural similarities in their active sites. CMK Chloromethylketone utilizes a different strategy by forming a covalent bond with the active serine residue in PC5/6, thereby stalling its protease function. Agmatine, while primarily a nitric oxide synthase inhibitor, can bind to the active site of PC5/6 due to its arginine-like structure, which allows it to compete with natural substrates for binding, thus inhibiting the enzyme's activity. Conantokin G, although a peptide that primarily inhibits NMDA receptors, can also impede PC5/6 by mimicking arginine-rich sequences, which are common in PC5/6 substrates, potentially blocking their cleavage. Leupeptin acts as a reversible inhibitor of serine and cysteine proteases, which includes binding to the catalytic site of PC5/6, preventing substrate hydrolysis. While Pepstatin A is typically an aspartic protease inhibitor, it can bind to sites that are similar between aspartic proteases and PC5/6, leading to a subsequent reduction in PC5/6's activity. E-64, known to irreversibly inhibit cysteine proteases, can indirectly lower PC5/6 activity by modifying the intracellular protease network, which can result in altered protease-protease interactions, impacting PC5/6 function. Lastly, Lactacystin, a specific proteasome inhibitor, can indirectly influence PC5/6 by preventing the degradation of its potential protein substrates, thereby affecting the enzyme's functional role within the cell.