Description
Tariquidar is an anthranilic acid derivative that binds to P-glycoprotein (K
d = 5.1 nM) and inhibits transport activity. It inhibits transport of vinblastine and paclitaxel in multidrug resistant CH
rB30 cells, increasing the steady state accumulation to non-P-glycoprotein-expressing multidrug sensitive cell levels (EC
50 = 487 nM). Tariquidar also enhances the distribution of its substrates, increasing the amount of substrate entering the CNS. When administered at doses of 2 and 6.25 mg/kg in mice in combination with the peripherally-restricted opioid loperamide, the latency to paw withdrawal in a hot plate assay increases, indicating that loperamide is transported into the CNS.
Uses
Tariquidar is a p-glycoprotein drug efflux pump inhibitor. Tariquidar inhibits the ATPase activity of P-glycoprotein, suggesting that the modulating effect is derived from the inhibition of substrate binding, inhibition of ATP hydrolysis or both.Tariquidar can be considered an ideal agent for testing the role of P-glycoprotein inhibition in cancer.
