Metabolic Stability

BOC Sciences has developed a comprehensive metabolic stability assay model, in collaboration with enzymology, cell, analytical biology and other platforms, to facilitate the drug discovery process.

Metabolic stability can be used to describe the speed and degree of compound metabolism, and is one of the main factors affecting pharmacokinetic properties, which affects the oral bioavailability, clearance rate and in vivo half-life of a compound. Low metabolic stability often indicates poor pharmacokinetic properties. Compounds with low metabolic stability have high in vivo clearance and low oral bioavailability.

Fig. 1 Effect of metabolic stability on pharmacokinetics

In the process of drug discovery, pharmacokinetic research is costly and time-consuming, which has become a bottleneck restricting the speed and success of new drug development. Therefore, detection of metabolic stability in the early stages of the drug discovery process and early elimination of compounds with poor metabolic properties will reduce the incidence of failure in later preclinical experiments and save development costs.

BOC Sciences provides high-quality liver microsome/S9/hepatocyte metabolic stability assays, metabolic enzyme phenotype assays to evaluate the metabolic stability of drugs in vitro, and to identify metabolites.

Liver Microsome Metabolic Stability Assay

The liver is the main metabolic organ of drugs and is rich in mixed-function oxidase systems involved in the first-phase and second-phase metabolism of drugs. The liver microsome model is an important in vitro model for studying drug metabolism. Liver microsome method for in vitro drug metabolism research has the advantages of convenient preparation, good reproducibility, easy preservation of enzyme mixture, easy optimization of incubation conditions, sensitivity and effectiveness, etc. BOC Sciences provides liver microsome metabolic stability assay services. Use the in vitro liver microsome incubation system to understand the intrinsic clearance rate or metabolite formation in vitro, and investigate the metabolic stability of the test compound. Results were characterized by UPLC, LC-MS/MS.

Hepatocyte Metabolic Stability Assay

Using the in vitro incubation method of primary hepatocytes, the metabolic reaction is carried out under simulated physiological environmental conditions (37°C) in vitro to identify metabolites or determine the intrinsic clearance rate in vitro. In contrast to the hepatic microsomal metabolic stability assay, no addition of NADPH or other cofactors is required in the hepatocyte metabolic response system. The determination of the metabolic stability of hepatocytes can better preserve and maintain the complete morphology of hepatocytes and the metabolic activity of hepatocytes in vitro, truly reflect the metabolism in vivo, and evaluate the overall cell metabolism of the test compound more extensively.

Fig. 2 Hepatocyte metabolic stability data display

S9 Metabolic Stability Assay

Using the animal liver S9 system as an in vitro metabolic model, use high performance liquid chromatography to detect the content of the test compound after incubation with animal liver S9, measure the intrinsic clearance in vitro or identify the metabolites formed. S9, the subcellular part of the liver, contains both phase I and phase II enzymes.

Metabolic Enzyme Phenotype Confirmation

BOC Sciences uses recombinant enzyme technology to study enzymes specifically involved in drug metabolism. Cytochrome P450s (CYPs) in phase I metabolism of drugs mediate the metabolism of most drugs. Glucuronosyltransferases (UGTs) are the main metabolic enzymes in phase II metabolism. Identify the metabolic enzyme phenotype of the drug, obtain the elimination ratio of its main metabolic enzymes, and clarify the related enzyme subtypes involved in the metabolic transformation of the drug in vivo, which is useful for studying the metabolic mechanism of drugs, predicting drug metabolic polymorphisms and drug-drug interactions, etc. aspect is of great significance.