pgp - publications

Predict more pgp - ligand interactions now!


1. J Med Chem. 2012 Apr 25. [Epub ahead of print]

Chalcogenopyrylium Compounds as Modulators of the ATP-Binding Cassette
Transporters P-glycoprotein (P-gp/ABCB1) and Multidrug Resistance Protein 1
(MRP1/ABCC1).

Ebert SP, Myette RL, Wetzel B, Conseil G, Cole SP, Sawada GA, Loo TW, Bartlett
MC, Clarke DM, Detty MR.

Twenty-seven chalcogenopyrylium derivatives varying in the heteroatom of the
pyrylium core and substituents at the 2-, 4- and 6-positions were examined for
their effect on human MRP1-mediated uptake of tritiated estradiol glucuronide
into inside-out membrane vesicles, their affinity for and ability to stimulate
the ATPase activity of purified human P-glycoprotein (P-gp)-His10, and their
ability to promote uptake of calcein AM and vinblastine in multidrug-resistant
cells. Differences in their effects on MRP1 and P-gp activity were noted and a
second set of thiopyrylium compounds with systematic substituent changes was
examined to refine these differences further. Derivatives with tert-butyl
substituents in the 2- and 6-positions had the lowest inhibitory activity toward
both transporters. Derivatives with thioamide functionality in the 4-position
were more active against MRP1 than derivatives with amide functionality.
Conversely, derivatives with amide functionality in the 4-position were more
active in P-gp than derivatives with thioamide functionality.

PMID: 22533905 [PubMed - as supplied by publisher]