MDCKII Monolayer Assays
| Service | Transporter | Technology | Probe Substrate | Reference Inhibitor | Barrier |
|---|---|---|---|---|---|
| MDCKII-BCRP substrate assessment | BCRP |
Monolayer Assay |
- | Ko134 or Ko143 | Blood-brain-barrier Intestinal Barrier Hepatic Barrier |
| MDCKII-BCRP inhibitor assessment | BCRP |
Monolayer Assay |
Prazosin, Chlorothiazide, Teriflunomide | Ko134 or Ko143 | Blood-brain-barrier Intestinal Barrier Hepatic Barrier |
| MDCKII-MDR1substrate assessment | MDR1/P-gp |
Monolayer Assay |
- | PSC833, Verapamil | Blood-brain-barrier Hepatic Barrier Renal Barrier Intestinal Barrier |
| MDCKII-MDR1inhibitor assessment | MDR1/P-gp |
Monolayer Assay |
Digoxin | PSC833 | Blood-brain-barrier Hepatic Barrier Intestinal Barrier Renal Barrier |
| MDCKII-mBcrp1 substrate assessment | Bcrp - mouse |
Monolayer Assay |
- | Ko134 or Ko143 | Blood-brain-barrier Intestinal Barrier Hepatic Barrier |
| MDCKII-mBcrp1 inhibitor assessment | Bcrp - mouse |
Monolayer Assay |
Prazosin | Ko134 or Ko143 | Blood-brain-barrier Intestinal Barrier Hepatic Barrier |
| MDCKII-OATP2B1/BCRP substrate assessment | BCRP OATP2B1 |
Monolayer Assay |
- | Estrone and Ko134 or Ko143 | Hepatic Barrier |
| MDCKII-OATP2B1/BCRP inhibitor assessment | BCRP OATP2B1 |
Monolayer Assay |
Estrone-3-sulfate | Estrone and Ko134 or Ko143 | Hepatic Barrier |
Description
The introduction of transporter transfected cell lines capable of forming tight cell layers has facilitated the investigation of single transporter interactions on monolayers. MDCKII (Madin-Darby canine kidney strain II cells) cell lines have been widely used as hosts for single and/or double transfections. The difference between efflux ratios on the transfected and parental cell lines is regarded as a sign of transporter mediated active uptake or efflux process.
SOLVO’s single transfectant MDCKII cell lines (MDR1/P-gp, BCRP, mBcrp) are excellent tools to investigate specific transporter interactions for medium to high permeability test articles. These service assays are offered in two modes, direct and indirect setups (effect of the test articles on the transport of the reporter substrate is measured).
Double transfected cell line (MDCKII-OATP2B1/BCRP) is able to mimic physiologically active vectorial transport processes such as the transport of digestive products across the intestinal epithelium from the luminal to the blood side, and the transport of bile salts and other steroid derivatives from the blood to the biliary side in hepatocytes. SOLVO’s double transfected cell line based monolayer studies include the corresponding two single transfectants and the parental cell lines as controls. Double transfected monolayers are suitable for performing both direct, vectorial transport studies and indirect, inhibitory studies (effect of the test articles on the transport of the reporter substrate is measured).
Studies available based on FDA and EMA Guidelines for Drug Interaction Studies and SOLVO’s recommendations:.
- Passive permeability in MDCKII transfectants and parentals (uni- or bidirectional)
- MDR1 substrate assessment in MDCKII-MDR1 transfectants (using specific MDR1 inhibitors)
- BCRP substrate assessment in MDCKII-BCRP transfectants (using specific BCRP inhibitors)
- Inhibitor assessments: for studying drug drug Interactions: MDR1: effect on digoxin transport, BCRP: effect on the transport of three probe substrates: prazosin, chlorothiazide and teriflunomide can be measured
MDCKII monolayer studies can be performed in different setups. SOLVO offers a number of standard setups, which differ in terms of the derivable information and cost. These standard setups serve as starting points to define the optimal final study parameters. All setups contain a standard number of controls (e.g. low permeability, high permeability, transporter function).
Study setups can be customized to suit your needs.
Learn more about the background of MDCKII-monolayer technology.
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