CYP Inhibition Screen Assay Using LC-MS/MS

Cytochrome P450 enzyme is the main drug metabolizing enzyme. It is mainly divided into five subtypes: CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4, which are related to more than 90% of drug metabolism and drug-drug interactions on the market and plays an important role in the activation of a variety of endogenous and exogenous substances. Inhibition of CYP450 activity caused by one drug often leads to metabolic disorders of the other drug, thereby causing toxic side effects. At the same time, CYP450 is associated with tumor formation and development, which can lead to the metabolism of cancerous substances and chemotherapeutic drugs, making CYP inhibitors widely used in tumor treatment and prevention research. Therefore, the determination of CYP450 inhibitory activity is of great significance to reduce adverse drug reactions caused by mixed medication and personalized medicine[1].

Figure 1 The regulatory feedback loop of the AHR and the CYP1 genes[1].

The drug probe substrates used by Profacgen include finacin, bupropion, diclofenac, mefentoin, dextromethorphan, midazolam, tolbutamide, and warfarin recommended by the FDA.We use LC-MS / MS to detect changes in the concentration of the probe substrate and its specific metabolites, determine the peak area of the corresponding metabolites, and combine the in vitro-in vivo and pharmacodynamic-pharmacokinetic models, determine the effect of drugs on CYPs inhibition, calculate the corresponding IC50, evaluate compound-mediated inhibition, and evaluate potential drug-drug interactions.

Advantages of CYP Inhibition Screen Assay Using LC-MS/MS:

1. Compared with MEIA and other methods, it is accurate, sensitive and reproducible;
2. Ability to accurately identify and quantify trace compounds in complex sample matrices

Profacgen has an excellent pharmacokinetic research team that can perform in vitro drug metabolism testing services for major institutes and institutions, including but not limited to: CYP inhibition test (single point inhibition, time-dependent inhibition), CYP induction experiment and identification of metabolic pathways. We always put your needs first, and if you have any questions about the results, we can help you verify. Profacgen is your ideal partner. If you are interested in our services, please feel free to contact us for more information.

Reference:

[1] Nebert, D., Dalton, T. The role of cytochrome P450 enzymes in endogenous signalling pathways and environmental carcinogenesis. Nat Rev Cancer 6, 947–960 (2006). https://doi.org/10.1038/nrc2015.