Tariquidar methanesulfonate, hydrate

>98%

Store at -20℃ for one year（Powder）；Store at 2-4℃ for two weeks；Store at -20℃ for six months after dissolution.

Tariquidar methanesulfonate hydrate,XR 9576,XR-9576

DMSO: ≥ 296 mg/mL; H2O: < 8.9 mg/mL

P-glycoprotein

Tariquidar (XR9576) methanesulfonate is a potent modulator of P-gp mediated -Vinblastine and -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 (EC50=487±50 nM). -Tariquidar binds to CHrB30 membranes with the highest affinity (Kd=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 -Vinblastine is increased in a dose-dependent fashion by the modulators XR9576 (EC50=487±50 nM). The MDR modulator Tariquidar is able to inhibit 60-70% of the vanadate-sensitive ATPase activity, with potent IC50 value of 43±9 nM. Tariquidar (XR9576) 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 Azidopine implying a direct interaction with the protein.

In mice bearing the intrinsically resistant MC26 colon tumors, coadministration of Tariquidar (XR9576) methanesulfonate potentiates the antitumor activity of Doxorubicin without a significant increase in 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.