Membrane transporters can have clinically relevant effects on the pharmacokinetics and pharmacodynamics of a drug in various organs and tissues by controlling its absorption, distribution and elimination. Together with metabolizing enzymes, they can drive a drug’s pharmacological action, as well as a drug can modulate transporter expression or activity, hence the importance of evaluating transporter-mediated drug-drug interactions recommended by the FDA guidelines. Genomembrane have developed transiently expressing ready-to-use cells to study FDA approved transporters (TransiPort). I had described this product range and their unique features in a previous post. I would like to introduce in this one 2 newly released cells overexpressing OATP1A2 and OATP2B1 transporters. [Read more…]
Sekisui XenoTech now offers human liver tissue microarrays (TMA) and a microsomal pool for studying and developing new treatments for fatty liver disease (FLD). The microsomes and arrays feature non-alcoholic steatohepatitis (NASH) and other liver tissue from the company’s Research Biobank . The initiative is part of Sekisui XenoTech’s ongoing commitment to furthering knowledge of hepatic diseases.
“Fatty liver disease is a highly pervasive condition that has a very significant impact on the health of modern society. We are supporting hepatology researchers with these collections of high-quality human tissues to advance basic knowledge of FLD and to develop new treatments for the illness,” explained Maciej Czerwinski, Ph.D., Sekisui XenoTech Director of Consulting who led the effort to establish the company’s research Biobank and develop the microarrays. [Read more…]
Over the years, Sekisui XenoTech has built up a strong expertise in preparing subcellular fractions for ADME applications.
There is a list of the fractions readily available for prompt delivery across Europe. However, the researcher’s specific needs in terms of species model, characterization or tissue for a particular metabolism study may not be met by the already available catalogue products. For this reason, the existing list is continuously expanding over the years in response to new demands.
Much experience has been gained by Sekisui Xenotech through interesting requests for custom tissue preparations from researchers. Here, I’d like to share some comments from the scientists at Xenotech involved in these preparations, to give you some insight in their customization capacities. [Read more…]
Recombinant CYPs are commonly used in ADME-Tox studies as in vitro tools, mostly for reaction phenotyping, enzyme inhibition screening, clearance and metabolite ID.
“Research has shown that rCYPs expressed in E. coli (Bactosomes) showed greater enzymatic activity compared with the equivalent enzymes expressed in insect cells (Supersomes). Similarly, most Bactosomes show greater turnover numbers when compared with the equivalent Supersomes. These results demonstrate that human rCYPs expressed in E. coli are frequently more active than the corresponding rCYPs expressed in insect cells» says Michael Voice from CYPEX. [Read more…]
HepatoSure® is a pool of human hepatocytes designed to facilitate your DMPK applications with a consistent hepatocyte product over time (years). HepatoSure® is best suited for both discovery and development of ADME-Tox study assays where generation and comparison of data is required. Let’s take a closer look, and you might like to benefit from our current offer to try these for yourself (see below). [Read more…]
Sekisui XenoTech has just established a method for high Aldehyde Oxidase and Xanthine Oxidase activity in pooled Human liver test systems.
These new test systems (Pooled Human Liver S9 and cytosol) have been prepared from tissue treated to preserve high Aldehyde Oxidase (AO) and Xanthine Oxidase (XO) activity, yet without significantly impacting major cytochrome P450 (CYP) activity. [Read more…]
These cell lines transiently express the current FDA and EMA recommended SLC drug transporters (eg. OCT1 and OCT2; OAT1 and OAT3; MATE1; MAT2K…). Conditioned as cryopreserved format, they provide flexibility for experimental planning and can be assayed in just 2 days.
Human and Animal Dermal S9 Fractions now available as standard products
Subcellular fractions are widely used in drug discovery and preclinical drug development to evaluate the in vitro metabolism of new therapeutics. Skin fractions are already available from tebu-bio as catalogue items for CD1 Mouse and IGS Sprague Dawley Rat.
A wide range of in vitro models are used in preclinical drug testing for the investigation of ADME-Tox (Absorption, Distribution, Metabolism, Excretion and oxicity) properties of New Chemical Entities (NCEs). The liver is the main organ with regards to ADME-Tox, it’s the place of more than 500 different functions, including: metabolism of lipids, carbohydrates, and vitamins, detoxification, production of bile, albumin, fibrinogen, globulin, etc (1). The liver lobule is composed of parenchymal cells (hepatocytes) and nonparenchymal cells (Kupffer cells, hepatic stellate cells, and sinusoidal endothelial cells).
Hepatocytes – the Gold Standard
Hepatocytes represent 80% of liver volume. Hepatocytes are commonly used in drug discovery and preclinical drug development to perform experiments requiring intact cellular systems. Intact hepatocytes contain the major hepatic drug-metabolizing enzymes required to study the four categories of xenobiotic biotransformation: hydrolysis, reduction, oxidation and conjugation.
Because of these enzymes, hepatocytes provide a viable and cost-effective alternative to in vivo testing. [Read more…]