Welcome! Thanks for your interest in CellPort Technologies™. We at Absorption Systems are excited to introduce this product line developed exclusively in our own laboratories. CellPort Technologies™ is a suite of novel, proprietary cell lines that provides exactly the in vitro data on P-gp interactions you need to include when submitting your NDA. 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, there is no interference from either canine or porcine P-gp.
By using each of the knockdown cell lines in parallel with wild-type Caco-2 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 and wild-type Caco-2 cells in parallel. 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.
In addition, each individual cell line has unique applications of its own. For example, CPT-B1, a BCRP-knockdown cell line, is a platform with which P-gp substrates can be identified without interference from BCRP (unlike wild-type Caco-2 cells). 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.
Click here for specific information about CPT-B1, the first of the CellPort Technologies™ cell lines, in which BCRP expression has been knocked down.
Click to contact Absorption Systems for more information. We look forward to hearing from you.
1FDA draft guidance on drug interaction studies: http://www.fda.gov/cder/guidance/6695dft.pdf