Cytochrome P450 Reaction Phenotyping
Creative Animodel is devoted to offering a portfolio of high-quality pharmaceutical contract services to accelerate the development of pharmaceutical industries. With advanced platforms and experienced expert team, our art-of-the-state cytochrome P450 reaction phenotyping service can deliver consistent and high-quality data with cost-efficacy.
The Importance of Cytochrome P450 Reaction Phenotyping
Cytochrome P450, also called CYP, is a superfamily involved with enzymatic biotransformation of drugs, toxins, carcinogens and normal endogenous compounds. Among the various Phase I and II drug-metabolizing enzymes, the cytochrome P450 superfamily is a major player and it has been estimated that approximately two thirds of marketed drugs are metabolized by this enzyme system. The human cytochrome P450 enzymes, found in the highest concentration in the liver, have versatile substrate specificities, and the results of in vitro cytochrome P450 reaction phenotyping are integrated with clinical data as a complete package submitted for regulatory review.
Understanding which enzymes account for the metabolism of your compounds helps:
• Predict potential drug interactions with likely co-administered drugs since CYPs inhibited or induced by other drugs are not desirable.
• Exclude unexpected drugs that are metabolized by polymorphic enzymes. Because drug metabolism involved with polymorphic enzymes gives rise to considerable variations between subjects.
Cytochrome P450 Reaction Phenotyping Assay at Creative Animodel
Incubate test compound with expressed individual cytochrome P450 isoforms at 37°C in the presence of co-factor, NADPH. The compound elimination is typically monitored over 45 minutes, and the supernatant after centrifugation is analyzed by LC-MS/MS at five time points (more upon request, for example, six time points over 60 minutes). And the compound clearance is corrected for any clearance observed in the negative control group. The results we deliver contain the clearance of compound at each time point, half life and the standard error half life for each isoform.
Our candidate P450 enzymes include CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4, UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A9, UGT2B7, UGT2B15, and more upon request.
Figure 1. (A). The percentage of remaining parent drug after metabolized by specific cytochrome P450 enzymes.
(B). Half life determination over 4 separate experiments.
• Advanced technical platforms and optimized methods
• A comprehensive portfolio of high quaility recombinant CYP enzymes
• Fast turnaround time: within 10 working days
• Over 10 years of pharmaceutical experience
• Custom service to meet your specific pharmaceutical demands
Creative Animodel is a leading pharmaceutical service contract provider equipped with integrated techniques and extensive expertise. Our cytochrome P450 reaction phenotyping service maintains compliance with regulatory guidelines and provides high-quality data with the flexibility to suit your specific requirements. Creative Animodel is always the best partner for your drug discovery.
Zhang H.; et al. Cytochrome P450 reaction-phenotyping: an industrial perspective. Expert opinion on drug metabolism & toxicology. 2007, 3(5): 667-687.