Sekisui XenoTech, LLC
10.0/10 Overall Rating
100% Positive
23 Orders Completed
Lenexa, Kansas, US
XenoTech offers in vitro and in vivo ADME and PK services including: drug-drug interactions (inhibition and induction), metabolism, reaction phenotyping, metabolite characterization, ID and stability, bioanalysis, transporter services, biologics, radiolabeled synthesis, QWBA and protein binding studies. We also offer a full catalog of in vitro ADME research products including hepatocytes, subcellular fractions, recombinant CYPs, kupffer cells, tritosomes, homogenate, media & reagents, etc.
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In vivo ADME lab offerings through Sekisui:
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Our Analytical Services group offers custom method validation, dose solution analysis, in vivo metabolite profiling studies and small-molecule bioanalytical services. The group's focus is on applying LC/MS technology to maximize both the quality and throughput of the data we generate to ensure that your project needs are met.
Toxicology Services: In vitro toxicity testing - XenoTech utilizes the MatTek EpiOcularâ„¢ platform, a validated test system for the classification of chemicals for ocular irritation according to the OECD (Organization for Economic Cooperation & Development) Test Guideline 492. The EpiOcularâ„¢ platform is a 3D tissue culture model comprised of non-keratinized epithelium prepared from normal human keratinocytes, which simulate the physiological properties of the cornea epithelium (RhCE) cells. The assay is able to assess test chemicals with a variety of physical properties including liquid, semi-solid, or waxy.
db/db Diabetic Mice
fa/fa Zucker Diabetic Rats
Overview
XenoTech's study design evaluates drug candidates as direct, time-dependent and metabolism-dependent inhibitors of CYP enzymes in human liver microsomes. Our design allows us to screen for inhibition due to the drug added to the test system as well as inhibition due to metabolites formed during preincubation. The design features low protein concentrations and short incubation times to minimize artifacts caused by protein binding, metabolic instability of the test article and excessive metabolism of the marker substrate. We offer various options for follow-up studies to support the further characterization of those drug candidates that are identified as potent direct or metabolism-dependent inhibitors (for example: Ki determinations, XTRA: XenoTech's Reversibility Assay, KI/kinact determinations).
Assay Selection
| Enzyme | Substrate |
|---|---|
| CYP1A2 | Phenacetin O-dealkylation |
| CYP2A6 | Coumarin 7-hydroxylation |
| CYP2B6 | Efavirenz 8-hydroxylation |
| CYP2B6 | Bupropion hydroxylation |
| CYP2C8 | Amodiaquine N-dealkylation |
| CYP2C8 | Paclitaxel 6-hydroxylation |
| CYP2C9 | Diclofenac 4´-hydroxylation |
| CYP2C19 | S-Mephenytoin 4´-hydroxylation |
| CYP2D6 | Dextromethorphan O-demethylation |
| CYP2E1 | Chlorzoxazone 6-hydroxylation |
| CYP3A4/5 | Testosterone 6β-hydroxylation |
| CYP3A4/5 | Nifedipine oxidation |
| CYP3A4/5 | Midazolam 1´-hydroxylation |
| CYP3A4/5 | Atorvastatin ortho-hydroxylation |
| CYP4A11 | Lauric acid 12-hydroxylation |
Test System
XenoTech's inhibition assays are typically performed with a dedicated pool of human liver microsomes (pool of 16) to provide Km and Vmax values for each marker substrate reaction. This allows the same pool of human liver microsomes (and often the same experimental conditions, for example, protein concentrations and incubation time) to be used to study all CYP enzymes of interest.
Incubation Conditions
Protein concentration ≤0.1 mg/mL
Incubation time: 5 minutes
Pre-incubation time (in the presence and absence of NADPH): 30 minutes
Results
Direct, time-dependent and metabolism-dependent IC50 values are determined from seven concentrations of the drug candidate.
XenoTech offers non-regulated small molecule bioanalysis services through its Analytical Services group. Highlights of XenoTech's bioanalytical capabilities include:
Toxicology Services: In vitro toxicity testing - XenoTech utilizes the MatTek EpiDermâ„¢ platform, a validated test system for the classification of chemicals for dermal irritation, according to the OECD Test Guideline 439. The EpiDermâ„¢ platform is a 3D tissue culture model comprised of reconstructed human epidermal (RhE) cells differentiated into keratinocytes, which stimulate the physiological properties of the human skin. The assay is able to assess test chemicals with a wide variety of physical properties including solids, liquids, semi-solids or waxy.
Cell viability following chemical exposure is measured using the MTT assay. The test article is then classified according to the UN GHS (United Nations Globally Harmonized System of Classification and Labelling Chemicals) according to viability following chemical exposure.
Pharmacology Services
"It was great working with XenoTech to complete a project for one of our biopharma clients. They were easy to work with and very professional. The client was very satisfied with the quality of services. We would definitely recommend them to other clients in the future!"
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