Efflux transporters are membrane proteins often involved in poor absorption and low oral bioavailability of drugs as those are kept out of the cells and effluxed back into the intestinal lumen. With this in mind, prediction of drug-transporter interactions during drug discovery and development is therefore of utmost importance as they can influence compounds pharmacokinetics and compromise drugs safety and efficacy.

Breast Cancer Resistance Protein (BCRP) transmembrane receptor is one of these efflux transporters the contribution of which should be investigated following scientific and regulatory requirements. Although BCRP was initially discovered as it conferred resistance to chemotherapeutics it is now known that it recognizes and transports a large number of structurally and chemically unrelated drugs and xenobiotics.

READYCELL has developed two specific cellular models of the epithelial barrier to test drug-BCRP interactions.

  • CacoReady, a cell-based kit containing differentiated and polarized Caco-2 cells that endoguenously express BCRP among other efflux transporters
  • PreadyPort that contains genetically-modified MDCK cells for the overexpression of a single transporter (BCRP).

CacoReady and PreadyPort in vitro kits are mostly applied for:

  • Substrate
  • Inhibitor-type interactions
  • Transport Induction studies.

Both kits are provided in a ready-to-use format and thank you to the patented gel-like Shipping Medium® they are available to deliver worldwide.

  Caco-2 MDCKII-WT MDCKII-BCRP Caco-2 MDCKII-WT MDCKII-BCRP
Reference Compound Papp cm/s (A-B) ER (Efflux Ratio)
Atenolol 0,15 ± 0,02 0,33  ± 0,11 0,33  ± 0,36 N/A 1,35 0,94
Metoprolol 19,42 ± 1,18 33,76 ± 1,82 21,77 ± 0,44 N/A 0,9 0,83
Dandolene 35.72 ± 1.83 1,49 ± 0,04 0,79 36,05
Prazosin 20,97  ± 0,26 4,39 ± 1,09 0,99 12,93
Table 1. Comparable permeability (Papp; cm/s) values and efflux ratio (Papp B-A/Papp A-B) for passive diffusion (atenolol and metoprolol) and BRCP substrates (Dandrolene and Prazosin) in the CacoReady and Preadyport cellular models.

 

For further information related to relevant pharmacological molecules, we recommend you to consult our product portfolio and contact our scientists at reagents@readycell.com.