MDCKII Monolayer Assays

Service Cell Line Transporter Technology Membrane Type Probe Substrate Read Out Reference Inhibitor Positive Control Dynamic Range
MDCKII-BCRP substrate assessment BCRP
Monolayer Assay
- Ko134 or Ko143
MDCKII-BCRP inhibitor assessment BCRP
Monolayer Assay
Prazosin, Chlorothiazide, Teriflunomide Ko134 or Ko143
MDCKII-MDR1substrate assessment MDR1/P-gp
Monolayer Assay
- PSC833, Verapamil
MDCKII-MDR1inhibitor assessment MDR1/P-gp
Monolayer Assay
Digoxin PSC833
MDCKII-mBcrp1 substrate assessment Bcrp - mouse
Monolayer Assay
- Ko134 or Ko143
MDCKII-mBcrp1 inhibitor assessment Bcrp - mouse
Monolayer Assay
Prazosin Ko134 or Ko143
MDCKII-rBcrp substrate assessment Bcrp - rat
Monolayer Assay
_ Ko134
MDCKII-rBcrp inhibitor assessment Bcrp - rat
Monolayer Assay
Prazosin Ko134
MDCKII-OATP2B1/BCRP inhibitor assessment BCRP
Monolayer Assay
Estrone-3-sulfate Estrone and Ko134 or Ko143
MDCKII-OAT1/BCRP substrate assessment BCRP
OAT1
Monolayer Assay
Probenecid and Ko134 or Ko143
MDCKII-OAT1/BCRP inhibitor assessment BCRP
OAT1
Monolayer Assay
p-Aminohippuric acid (PAH) Probenecid and Ko134 or Ko143
MDCKII-OAT3/BCRP inhibitor assessment BCRP
OAT3
Monolayer Assay
estrone-3-sulfate, methotrexate, chlorothiazide probenecid, Ko134
MDCKII-OAT3/BCRP substrate assessment BCRP
OAT3
Monolayer Assay
estrone-3-sulfate, methotrexate, chlorothiazide probenecid, Ko134
MDCKII-OCT2/MATE1 inhibitor assessment MATE1
OCT2
Monolayer Assay
TEA, metformin cimetidine, pyrimethamine
MDCKII-OCT2/MATE1 substrate assessment MATE1
OCT2
Monolayer Assay
TEA, metformin cimetidine, pyrimethamine
MDCKII-OCT2/MATE2K inhibitor assessment MATE2
OCT2
Monolayer Assay
Metformin, TEA pyrimethamine, cimetidine
MDCKII-OCT2/MATE2K substrate assessment MATE2
OCT2
Monolayer Assay
pyrimethamine, cimetidine
MDCKII-OATP2B1/BCRP substrate assessment OATP2B1
Monolayer Assay
Ko143

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.