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.
Definition
ChEBI: Tariquidar is a member of benzamides.
Biochem/physiol Actions
Specific inhibitor of MDR-1 (P-gp)
References
[1] CATHERINE MARTIN. The molecular interaction of the high affinity reversal agent XR9576 with P-glycoprotein[J]. British Journal of Pharmacology, 2009, 128 2: 403-411. DOI:
10.1038/sj.bjp.0702807[2] EDNA F CHOO. Differential in vivo sensitivity to inhibition of P-glycoprotein located in lymphocytes, testes, and the blood-brain barrier.[J]. Journal of Pharmacology and Experimental Therapeutics, 2006, 317 3: 1012-1018. DOI:
10.1124/jpet.105.099648
