Cyp2c37 Inhibitors

Chemical inhibitors of Cyp2c37 include a variety of compounds that can interact with the enzyme to reduce its activity through different mechanisms. Sulfaphenazole, for instance, is a selective CYP2C inhibitor that competes with the natural substrates of Cyp2c37, binding to its active catalytic site and thereby reducing the enzyme's metabolic function. Similarly, the flavonoid quercetin also binds to the active site of Cyp2c37, preventing the enzyme from interacting with its intended substrates. Clopidogrel, through its metabolism, can form a reactive metabolite that irreversibly binds to Cyp2c37, resulting in a sustained decrease in enzyme activity. Montelukast operates on the same principle by competing for the substrate binding sites on Cyp2c37, thus impeding the enzyme's ability to metabolize other compounds effectively.

Further, inhibitors such as fluconazole and ketoconazole target the heme group within Cyp2c37. Fluconazole binds to this group, which is vital for the enzyme's catalytic action, thus inhibiting its function. Ketoconazole similarly interferes with the heme iron center of Cyp2c37, blocking the enzymatic processing of its substrates. Triclabendazole and methoxsalen employ a slightly different approach; triclabendazole inhibits by binding to the active site of Cyp2c37, reducing its activity, while methoxsalen acts as a mechanism-based inhibitor forming a covalent bond with the active site, leading to irreversible inhibition. Phenylbutazone and diclofenac both inhibit Cyp2c37 through competitive inhibition by occupying the active site and preventing substrate metabolism. Diclofenac achieves this through a metabolite that binds irreversibly to the enzyme. Chloramphenicol inhibits by directly binding to the active site of Cyp2c37, while proadifen, or SKF-525A, reduces the enzyme's catalytic efficiency by non-selectively binding to multiple sites on Cyp2c37. These chemical interactions all serve to inhibit the normal function of Cyp2c37 by preventing its usual metabolic processing of substrates.