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BCRP expression in red blood cells? #248
I try to develop a model for a BCRP substrate drug and recently found the following publication: https://www.ncbi.nlm.nih.gov/pubmed/29098941
Many thanks in advance,
I do not see a way to implement it in PK-Sim.
In MoBi, you have to "express" the transporter in the RBC. For this, create a simple PK-Sim model with any protein expressed in RBC (as you can do for enzymes). This will be your template.
In your model with BCRP, in the molecule start values - building block, select the check-box "Is Present" for BCRP in all BloodCells-containers (do not forget the mucosa-tissues!). In the parameter start values - building block, change the values of "Relative expression in blood cells" and "relative expression in blood cells (normalized)" to the value according to your calculated expression values. Then, for all "BloodCells"-compartments, set the values of the parameters "Relative expression", "Relative expression (normalized)", and "Relative expression out." to the same formulas as the RBC-expressed protein from the template model you created in PK-Sim.
Finally, you have to create a new transport process in the molecules-buidling block. Expand all molecules that are substrates of this transporter, find BCRP, right-click on it and select "Create transport". You then have to adjust the "Properties" (from RBC to plasma) and define a new reaction rate formula.
@PavelBal: Thank you very much for the detailed explanation! I recently found the time to test it and it worked like a charm. However, let me add a few experiences in case someone want to reproduce the method:
Hope it helps! If someone has a question about this procedure feel free to ask.
Here are the files: building_blocks.zip
PS: I think this issue can be closed now.