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.
In this post, I’d like to introduce the new Human liver Lysosomes developed by Sekisui-Xenotech that are indeed opening a new era in catabolism models.
Sekisui Xenotech’s Liver Research BioBank is committed to providing high-quality but affordable diseased & normal pre-lysate tissues for research applications. These tissues are collected with the initial intent for transplant, making this Liver Biobank an ideal tool for advanced basic medical research and new drug developments.
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). [Read more…]
The inadequacy of animal models to predict human biology in the drug development process is becoming increasingly clear, due to species differences in uptake and metabolism at both cellular and organ levels.
As a result, there is a need for more human model systems to be incorporated earlier in research and development.
Innovative concepts such as “body on a chip” have been introduced, but the complexity and miniaturization of many of the formats has limited applicability on a commercial scale.
SciKon is developing tools that better recapitulate biological systems in bench-top cell culture formats, which are amenable to mass manufacturing (introduced recently in the post Cell Signaling isn’t static…your cell culture shouldn’t be either!). [Read more…]
Complex cell culture systems are emerging as key tools to improve physiological relevance of in vitro assay systems. There have been two main ways by which investigators attempt to improve mimicking of physiological conditions in cell and tissue culture. The first is to develop more complex model systems where two or more cell types are co-cultured in a 3D structure either separated by membranes or in spheroids . The second is to incorporate fluidic-flow where the motion of the media itself has been shown to improve metabolic function and lifespan [2,3].
Despite the success of better recapitulating function at the cellular level using these two methods, neither of these approaches addresses the issue of the non-linear nature of the drug or toxicant exposure as is observed in an in vivo system . As a result, the capacity to accurately predict in vivo pharmacokinetics and pharmacodynamics still falls short reaching at best 60-70% accuracy [5,6].
So what’s new in this area? We were interested to discover the following system, which we think will be of interest to many researchers. Let’s take a closer look at the characteristics and how it can be used. [Read more…]
Transporters have become increasingly important in drug development due to the major role they play in absorption, distribution and excretion of endogenous and exogenous compounds, as transporter-mediated drug-drug interactions (DDI) are associated with potential toxicological and pharmacological consequences. As shown in numerous publications, the effects of transporters on the pharmacokinetics of several drugs and associated DDI have been reported. Consequently, recent guidance documents released by the US FDA and European Medicines Agency (EMA) emphasize the importance of evaluating the potential of new drug candidates for transporter-mediated DDI.
Solute carrier (SLC) transporters are located in the small intestine, liver, kidney, blood-brain barrier, and so on. They play a role in the up-take of various drugs, as well as endogenous nutrients into cells and thus may influence the ADME properties of, or indeed adverse reactions to, a compound of interest. Thus, investigation of SLC transporters is expected to be helpful during drug development. [Read more…]
Rat liver tritosomes are hepatic lysosomes that have been loaded with Tyloxapol (Triton WR 1339), a non-ionic surfactant. Tyloxapol is taken up by hepatocytes through endocytosis and is trafficked to lysosomal compartments. Tyloxapol containing lysosomes exhibit decreased density and can be more efficiently isolated away from contaminating cellular organelles that have overlapping densities with native lysosomes (1-3). [Read more…]
The urogenital system is the organ system of the reproductive organs and the urinary system. These are grouped together because of their proximity to each other, their common embryological origin and the use of common pathways, like the male urethra.
Today, I’ll be taking a look at human primary cells derived from urogenital organs (and in one of my next posts, we’ll explore models for the digestive system.