MDCKII Monolayer Assays

Service Cell Line Transporter Technology Membrane Type Probe Substrate Read Out Reference Inhibitor Positive Control Dynamic Range
Abcb1KO-MDCKII-MDR1 - Digoxin MDR1/P-gp
Monolayer Assay
Digoxin Valspodar
MDCKII-Bcrp- Cynomolgus monkey Bcrp - cynomolgus monkey
Monolayer Assay
Prazosin Ko143
MDCKII-BCRP - Chlorothiazide BCRP
Monolayer Assay
Chlorothiazide Ko143
MDCKII-BCRP - Prazosin BCRP
Monolayer Assay
Prazosin Ko143
MDCKII-BCRP - Teriflunomide BCRP
Monolayer Assay
Teriflunomide Ko143
MDCKII-Bcrp- Rat Bcrp - rat
Monolayer Assay
Prazosin Ko143
MDCKII-Bcrp1- Mouse Bcrp - mouse
Monolayer Assay
Prazosin Ko143
MDCKII-Mdr1- Cynomolgus monkey Mdr1 - cynomolgus monkey
Monolayer Assay
Digoxin Valspodar
MDCKII-MDR1 - Digoxin MDR1/P-gp
Monolayer Assay
Digoxin Valspodar
MDCKII-MDR1 - Quinidine MDR1/P-gp
Monolayer Assay
Quinidine Valspodar or Verapamil
MDCKII-OATP2B1/BCRP BCRP
Monolayer Assay
Estrone 3-sulfate (E3S) Ko143 and Estrone
MDCKII-OCT2/MATE1 - Metformin MATE1
OCT2
Monolayer Assay
Metformin Cimetidine and Pyrimethamine
MDCKII-OCT2/MATE1 - Tetraethylammonium chloride (TEA) MATE1
OCT2
Monolayer Assay
Tetraethylammonium chloride (TEA) Cimetidine and Pyrimethamine
MDCKII-OCT2/MATE2K - Metformin MATE2
OCT2
Monolayer Assay
Metformin Cimetidine and Pyrimethamine
MDCKII-OCT2/MATE2K - Tetraethylammonium chloride (TEA) MATE2
OCT2
Monolayer Assay
Tetraethylammonium chloride (TEA) Cimetidine and Pyrimethamine

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, inhibitor and substrate assessment. (In the inhibitor assessment experiments the effect of the test articles on the transport of the reporter substrate is measured).

Double transfected cell lines are able to mimic physiologically active vectorial transport processes such as the transport of bile salts and other steroid derivatives from the blood to the biliary side in hepatocytes (MDCKII-OATP2B1/BCRP), or vectorial transport of negatively charged organic molecules across kidney epithelium cells (MDCKII-OAT1/BCRP). In addition, the OAT1-BCRP model can be used to detect compounds with potential for causing hyperuricemia. 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/probe 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.