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…]
NADPH is a critical cofactor supporting numerous biochemical reactions. In ADME-Tox studies, NAD(P)H regeneration is strongly recommended when using drug metabolizing enzymes (ex. Cytochrome P450 (CYP), Flavin-containing MonoOxygenases (FMO)), Recombinant CYPs (incl. bactosomes) or cellular fractions (Microsomes, S9). Currently, the most simple and cost-effective way to regenerate the NAD(P)H in situ and enzymatically is to use the commercially-available RapidStart™ NADPH Regenerating System (Xenotech-Sekisui).
RapidStart uses an enzymatic reaction that changes NADP to NADPH, which is then oxidized by CYPs back to NADP, and the cycle continues…
Following up on my series of posts based on Dr Chris Bohl’s work at Sekisui Xenotech, in this post I invite you to take a look at the work he has published, together with Dr Christopher Seib, Maciej Czerwinski, Zell Woodworth and David Buckley, Ph.D., illustrating the characterization of isolated human liver lysosomes, and validating them as test systems for in vitro assessment of catabolic stability of biologics drugs entering the cell by the endosomal–lysosomal pathway.
In a few forthcoming posts, I’d like to share several short articles published by Dr Chris Bohl of Sekisui Xenotech, a technical expert in the field of ADME-Tox tools and applications. I feel they may be of special interest to researchers working in the field of ADME-Tox studies.
Today, we’ll take a look at compounds that exhibit high metabolic stability in hepatocytes and subcellular fractions (S9, microsomes and cytosol), as these can be a challenge for ADME scientists. [Read more…]
Sekisui Xenotech’s Research BioBank provides you with normal and diseased human liver tissue samples for scientific investigation. Tissues are collected with the initial intent for transplant, thus making them perfect candidates to advance basic medical science and contribute to the development of new treatments.
The care taken to preserve viability of the tissue intended for transplantation distinguishes these Research Biobank specimens from samples collected at a typical post-mortem, usually compromised by several hours of a warm ischemia. So what are the other benefits of the biobank? [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…]