Tariquidar methanesulfonate, hydrate is a potent and specific P-glycoprotein (P-gp) inhibitor(Kd of 5.1 nM).

Tariquidar methanesulfonate, hydrate (XR9576 methanesulfonate, hydrate) is a potent P-gp mediated [3H]-Vinblastine modulator and [3H]-Paclitaxel transport as it increases the steady-state accumulation of these cytotoxics in CHrB30 cells to levels observed in non-P-gp-expressing AuxB1 cells with EC50 of 487±50 nM. [3H]-Tariquidar binds to CHrB30 membranes with the highest affinity with Kd of 5.1±0.9 nM, n=7 and a binding capacity (Bmax) of 275±15 pmol/mg membrane protein. In contrast to the parental cell line, the accumulation of [3H]-Vinblastine is increased in a dose-dependent fashion by the modulators XR9576 with EC50 of 487±50 nM. The MDR modulator Tariquidar is able to inhibit 60-70% of the vanadate-sensitive ATPase activity(IC50 of 43±9 nM)[1]. Tariquidar potentiates the cytotoxicity of several drugs including Doxorubicin, Paclitaxel, Etoposide, and Vincristine; complete reversal of resistance is achieved in the presence of 25-80 nM Tariquidar. Tariquidar is a potent inhibitor of photoaffinity labeling of P-gp by [3H]Azidopine implying a direct interaction with the protein[2].

In mice with intrinsically resistant MC26 colon tumors, co-administration of hydrated Tariquidar mesylate (XR9576 mesylate, hydrate) can enhance the antitumor activity of doxorubicin without significantly increasing toxicity; maximum potentiation is observed at 2.5-4.0 mg/kg dosed either i.v. or p.o. In addition, coadministration of Tariquidar (6-12 mg/kg p.o.) fully restores the antitumor activity of Paclitaxel, Etoposide, and Vincristine against two highly resistant MDR human tumor xenografts (2780AD, H69/LX4) in nude mice. Tariquidar is found to also significantly potentiate the antitumor activity of doxorubicin against s.c. MC26 tumors in vivo[2].