Reaction Phenotyping

Reaction phenotyping research is primarily used to identify the enzymes responsible for the biotransformation of compounds. BOC Sciences can provide in vitro reaction phenotyping research that meets regulatory expectations, including CYP enzymes, non-CYP enzymes, and conjugated enzymes. Our reaction phenotyping characterization provides metabolic data information for the sample to be tested, which can be used to assess victim DDI potential and provide useful information for clinical study design.

Metabolic Enzyme Phenotyping Study

In preclinical studies of new drugs, the metabolic enzyme phenotypes of drugs should be identified and the elimination ratios of their major metabolic enzymes should be obtained to provide important information for drug-drug interaction studies.

Enzyme Phenotype Identification of CYP450 Enzymes

CYP450 is a superfamily of heme-containing proteins that widely exists in humans and mammals, and is mainly involved in the oxidative metabolism of drugs, environmental compounds and endogenous substances. CYP450 is the predominant metabolic enzyme in the human body, and about 60% of drug metabolism is mainly mediated by the CYP450 enzyme family. Based on the importance of the relevant enzyme isoforms in drug metabolism, CYP450 can be classified into the following three categories:

1. Most major CYP450, including CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4.
2. Major CYP450, including CYP2B6, CYP2C8, and CYP3A5.
3. Secondary CYP450, including CYP1A1, CYP1B1, CYP2A6, CYP2E1, CYP2J2, and CYP4A11, etc. Food and Drug Administration recommends identification of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A and other subtypes.

Currently, three methods are used to identify the enzyme phenotype of CYP450: selective inhibition, recombinant human CYP450 isozyme assay, and correlation analysis.

Enzyme Phenotype Identification of UGT Enzymes

UGT is a class of membrane proteins located in the endoplasmic reticulum inner membrane that catalyzes the removal and transfer of glucuronide from uridine diphosphate glucuronide to receptor molecules to generate glucuronide conjugates for receptor molecules. UGT plays an important role in drug metabolism in humans, second only to CYP450.

UGT enzyme family can also be divided into several families and subfamilies. The UGT enzymes involved in the metabolism of exogenous substances mainly belong to the UGT1A and UGT2B subfamilies, including UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A9, UGT2B7 and UGT2B15. Unlike the CYP450 enzyme family, the identification of the enzyme phenotypes of the UGT enzyme family is limited by many factors, and a more mature research system has not yet been developed.

Reaction Phenotyping Solutions

Deliverables

• Our reaction phenotyping will identify the enzymes and extent of metabolism responsible for the in vitro metabolism of the test article.
• Determine the kinetics of test article disappearance and/or metabolite formation.
• In vitro metabolism assessment identifies the major enzymes involved and alerts you to potential in vivo clearance mechanisms responsible before first-in-human trials.

Our Advantages

Comprehensive service types

We offer a wide range of services from screening to reporting, making it a convenient one-stop shop for customers. Multiple automated instrument platforms enable continuous throughput improvement.

High throughput and fast data delivery

Relying on strong technical capabilities, excellent operational services and constantly improving experimental throughput, we can save time and cost for our customers.

High-quality experimental data

The introduction of an automated platform can reduce human errors, reduce experimental errors and improve data quality.

Experienced Researchers

Our team of experts has extensive experience in ADME studies, providing the most effective data in the shortest possible time, saving resources and accelerating the development process for drug discovery projects.