A 4-aminobenzoic acid derivative as novel lead for selective inhibitors of multidrug resistance-associated proteins.

Article Details

Citation
Copy to clipboard

Leyers S, Hacker HG, Wiendlocha J, Gutschow M, Wiese M

A 4-aminobenzoic acid derivative as novel lead for selective inhibitors of multidrug resistance-associated proteins.

Bioorg Med Chem Lett. 2008 Sep 1;18(17):4761-3. doi: 10.1016/j.bmcl.2008.07.127. Epub 2008 Aug 3.

PubMed ID
18707884 [ View in PubMed
]
Abstract

We present a novel lead for inhibitors of multidrug resistance-associated proteins (MRPs). Compound 1 (4-[(5,6,7,8-tetrahydro-4-oxo-4H-[1]benzothieno[2,3-d][1,3]thiazin-2-yl)amino]ben zoic acid) was about six times more potent than the known inhibitor MK571 at MRP1, while at MRP2 its effect was similar to that of MK571. Structural analogs were also evaluated. Among them, compound 2, sharing the 4-aminobenzoic acid substructure with 1, also inhibited MRP1. Both derivatives were inactive against P-gp. It can be concluded that their carboxyl group is needed for inhibition of MRPs and accounts for the selectivity of these compounds.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
CyclosporineCanalicular multispecific organic anion transporter 1IC 50 (nM)13600N/AN/ADetails
IndomethacinCanalicular multispecific organic anion transporter 1IC 50 (nM)235000N/AN/ADetails
IndomethacinMultidrug resistance-associated protein 1IC 50 (nM)12000N/AN/ADetails