In Vitro ADMET Products:
1. Primary Hepatocytes, microsomes and S9 fraction of liver and other organs of humans and animals;
2. Phase I and Phase II Recombinant enzymes
3. Recombinant human and animal drug transporters;
4. Various substrates, metabolites, inhibitors and inducers for ADMET research.
Primary hepatocytes are functional units with intact cellular structures. It has intact nuclear and cytoplasmic components and can perform transcription, translation, protein localization and metabolic enzyme activity of metabolic enzyme genes. Primary hepatocytes are widely used in drug phase I metabolism, phase II metabolism test, induction test, cell-based inhibition test and hepatotoxicity test, hepatocyte surface drug transporter inhibition and substrate test. Human hepatocytes cryopreserved by liquid nitrogen are ideal for predicting metabolism and transporter metabolism in humans with the convenience and good repeatability of the FDA's latest guidelines.
Microsomes are subcellular components prepared by differential centrifugation of organs such as the liver, intestines, and kidneys. They are part of the endoplasmic reticulum of the organelle, and this part expresses a wide variety of proteins. In particular, liver microsomes have intact phase I metabolic enzymes (such as cytochrome P450 <CYP450 isoforms>, flavin monooxygenase <FMOs>, monoamine oxidase <MAO>, etc.), phase II metabolic enzymes (such as glucuronyltransferase <UGTs>, sulfate transferase <SULT>, esterase, etc. It can reflect the metabolism of drugs in most people. It is a research tool for predicting metabolic and inhibition tests in humans as specified by the FDA's latest guidelines.
The S9 fraction is the product of an organ tissue homogenate used in biological assays. The S9 fraction is most frequently used in assays that measure the metabolism of drugs and other xenobiotics. It is defined as the "Supernatant fraction obtained from an organ (usually liver) homogenate by centrifuging at 9000 g for 20 minutes in a suitable medium; this fraction contains cytosol and microsomes." The microsomes component of the S9 fraction contain cytochrome P450 isoforms (phase I metabolism) and other enzyme activities. The cytosolic portion contains the major part of the activities of transferases (phase II metabolism). The S9 fraction is easier to prepare than purified microsomes. The S9 fraction has also been used to assess the metabolic stability of candidate drugs.
The cytoplasm is a liquid part dissolved in intact cells, referred to as Cytosol, which is the supernatant fraction (precipitated as microsomes) when S9 is centrifuged at 109000g, mainly containing proteins dissolved in the cell serum, and various cellular contents. Substances, such as NADPH, UDPGA, PAPS, etc., act as cofactors for initiating drug metabolism.
Plasma, the supernatant of the blood after centrifugation under the action of an anticoagulant, is a good tool for protein binding experiments.
Recombinant enzyme is a single type of enzyme that has been purified by gene cloning and expression using molecular biology methods. It is convenient to verify the metabolic pathway of drugs in the study of metabolic phenotype and calculate the contribution of sub-enzymes involved in drug metabolism. Compared with the mixing of various metabolic sub-enzymes in the natural proportion in the microsomes, it is a single subtype of overexpression, which is easier to amplify the contribution of the sub-enzyme to metabolism.
A transporter is a transmembrane protein that binds to intracellular or extracellular substances and ingests or pumps them out of the cell, mainly on the surface of cells such as the intestine, liver, kidney, and brain. The transporter protein is only involved in the transport of the substance and does not alter the chemical structure of the substance. The transporter's changes in drug transport properties are important factors in the interaction of clinical drugs, and are an important part of the study of drug-in vitro interactions in new drugs.
The culture medium is an important component for culturing primary hepatocytes, and contains Thawing Media, Plating Media, and Incubation Media, which can maintain the Biological function of primary hepatocytes in in vitro assays.
Includes probe substrates for each drug-metabolizing enzyme, corresponding metabolites, inhibitors, inducers, substrate and inhibitors associated with each transporter, and corresponding coenzymes required for enzymatic reactions, including the FDA Drug Interactions Guidelines.