CYP2C9 is an enzyme protein. The enzyme participates in the metabolism of exogenous substances (including drugs) and endogenous compounds (including fatty acids) through oxidation. Importantly, CYP2C9 is the most abundant CYP2C subfamily enzyme in the human liver, and it is also the most important contributor of this subfamily to drug metabolism. Obviously, CYP2C9 is responsible for the metabolism of up to 15% of small molecule drugs. Particularly, CYP2C9 is the main enzyme responsible for metabolic clearance of several clinically used drugs with a narrow therapeutic index. Therefore, individual differences in CYP2C9 protein expression and activity may affect the efficacy and safety of drug therapy.

Cytochrome P450 (CYP) enzymes are relevant to the metabolism of different substances Xenobiotics and several clinically important drugs. Interestingly, CYP is an enzyme that uses iron-oxidizing substances and can metabolize a variety of xenobiotics. Meanwhile, CYP enzymes are involved in a variety of reactions, including O-dealkylation, S-oxidation, epoxidation, and hydroxylation. Most CYP enzymes exhibit a large number of effects similar to those of proinflammatory cytokines and IFN. CYP2C9 can mediate the oxidation of several important drugs. Polymorphisms leading to reduced enzyme activity are common in the CYP2C9 gene. Nonetheless, CYP2C9 is also relevant to the metabolism of several important psychoactive substances. Here, we will introduce a specific inhibitor of CYP2C9, Sulfaphenazole.

Sulfaphenazole is a Specific CYP2C9 Inhibitor with Antibacterial and Antimicrobial Activity.

Above all, Sulfaphenazole is a specific inhibitor of CYP2C9 which blocks atherogenic and pro-inflammatory effects of linoleic acid (increase in oxidative stress and activation of AP-1) mediated by CYP2C9. Besides, Sulfaphenazole acts as an antibacterial and antimicrobial.

Next in importance, Sulfaphenazole does not inhibit the oxidation of JWH-018 or AM2201 at 50 μM. Specifically, increasing the concentration of Sulfaphenazole (0.5 μM, 5 μM, and 50 μM) inhibits JWH-018 ω-oxidation by ~20, 80, and 100%.

All in all, Sulfaphenazole is a specific inhibitor of CYP2C9.


Chimalakonda KC, et al. Drug Metab Lett. 2013 Mar;7(1):34-8.