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CellPort Technologies®
We are excited to introduce this product line developed exclusively in our own laboratories. CellPort Technologies is a suite of unique preclinical models that provide definitive data to predict clinical drug-drug interactions (DDIs) involving drug transporters. To create CellPort Technologies, we started with a stable clone of human Caco-2 cells and used RNA interference to knock down the expression of one efflux transporter at a time. The cell lines are designed to be used in the bidirectional transport assay format designated as "definitive" by the FDA1. Unlike some other cell lines that can be used in this assay format, they are fully human assay systems: there is no interference from either canine or porcine P-gp.
"We have not found any other in vitro model we could use to answer [our] question."
Says Tommy Andersson of AstraZeneca R&D Mölndal, Sweden, "The metabolites had to be generated in the cells in order to see whether they were transported. To our knowledge, no other in vitro model has the combination of human drug transporters, either overexpressed or silenced, with the metabolic capacity to generate metabolites of ximelagatran inside the cells.” This is just one example of an application of CellPort Technologies.
Absorption Systems Video Trailers
By using each of the knockdown cell lines in parallel with control cells, we can determine, by process of elimination, for which efflux transporter(s), if any, your compound is a substrate. We run bidirectional transport assays with each CellPort cell line in parallel with control cells. A substrate of BCRP, for example, would have a high efflux ratio in wild-type cells and in each cell line in which a different efflux transporter was knocked down, but a low efflux ratio in the cell line in which BCRP was knocked down. For an illustration of this approach, click here to download a poster presented at the 2008 North American ISSX meeting in San Diego.
In addition, each individual cell line has unique applications of its own. For example, CPT-B1, a BCRP knockdown cell line, is also a platform with which P-gp substrates can be identified with less interference from BCRP. To identify P-gp substrates, we run bidirectional transport assays with test compounds in the presence and absence of cyclosporin A (CsA), a P-gp inhibitor. P-gp substrates have a high efflux ratio in the absence of CsA and an efflux ratio near 1 in the presence of CsA. Because BCRP expression has been knocked down, we can be sure that positives in this assay are P-gp substrates.
You might ask "How does the FDA feel about CellPort Technologies?" Good question! Suffice to say that the agency's degree of interest is indicated by the fact that it has helped fund the development of the models via Phase I and Phase II SBIR grants.
Click here for specific information about CPT-B1, the CellPort Technologies cell line, in which BCRP expression has been knocked down.
Click to contact Absorption Systems for more information. We look forward to hearing from you.
View our technical video on CellPort Technologies.
1FDA draft guidance on drug interaction studies: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM072101.pdf
Related Literature
This assay is used to determine the P-gp interaction with a test compound using CellPort™ CPT-B1 BCRP-knockdown cell monolayers in both the presence and the absence of a P-gp inhibitor.
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This assay is used to determine the BCRP interaction with a test compound using CellPort™ CPT-B1 BCRP-knockdown cell monolayers and wild-type Caco-2 cell monolayers.
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Brochures
A unique, more definitive test system for identifying BCRP and P-gp substrates
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Services and products based on the novel, proprietary CellPort Technologies
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Introduction to CellPort Technologies, a more definitive drug transporter assay system
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In vitro testing to identify P-gp substrates, inhibitors and inducers
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