Pgp inhibition comparison for Fluorosome-trans-pgp and R123 efflux from MDR1 cells.

Comparison of Pgp inhibition results for Fluorosome-trans-pgp and R123 efflux from MDR1 cells.

A recent publication (Broccatelli et al., J. Med. Chem. 54: 1740-1751 (2011)) described an in silico model for pgp inhibition of a large set of structures. Among the compounds described, ten drugs were tested for Pgp inhibition by observing their effect on efflux of the fluorescent marker Rhodamine 123 (R123) by mouse T lymphoma cell line L5178Y transfected with recombinant MDR1. We tested  seven of these compounds by the Fluorosome-trans-pgp technique using 50 µl volumes in 384 well plates. The results of both assays are presented in the Table. Also included in the Table are compound classifications as predicted by the proposed model. It is clear that inhibition potencies are highly correlated and that inhibition by “weak inhibitors” and even “non-inhibitors” can be readily quantitated by Fluorosome-trans-pgp.