Tariquidar methanesulfonate hydrate (XR9576 methanesulfonate hydrate) is a selective and potent P-glycoprotein drug efflux pump inhibitor with potential anticancer activity that induces P-glycoprotein inhibition of the blood-brain barrier in rats.

P-gp:487 nM (EC50), ATPase (vanadate-sensitive):43 nM, CHrB30 membranes:5.1 nM (Kd), CHrB30 membranes:275 pmol/mg (Bmax)

Tariquidar methanesulfonate hydrate is a potent P-gp-mediated inhibitor of [³H]-vincristine and [³H]-paclitaxel transport that elevates the accumulation of these drugs in CHrB30 cells to a level similar to that of AuxB1 cells that do not express P-gp (EC50 of 487 nM) . [³H]-Tariquidar methanesulfonate hydrate showed high binding affinity (Kd of 5.1 nM) on CHrB30 membranes and had a maximum binding capacity (Bmax) of 275 pmol/mg membrane protein. Tariquidar methanesulfonate hydrate significantly increased the intracellular accumulation of [³H]-vincristine (EC50 of 487 nM) through a dose-dependent effect compared to its parental cells. In addition, the multidrug resistance modifier Tariquidar methanesulfonate hydrate inhibited 60-70% of vanadate-sensitive ATPase activity with an IC50 of 43 nM. [1]

In a mouse model harboring MC26 colon tumors (with intrinsic resistance), combination with Tariquidar methanesulfonate hydrate potentiated the antitumor effects of doxorubicin without a significant increase in toxicity; potentiation was maximal at doses of 2.5-4.0 mg/kg (which can be administered intravenously or orally). The synergistic effect was maximized at a dose of 2.5-4.0 mg/kg (which can be administered intravenously or orally). In addition, oral administration of Tariquidar methanesulfonate hydrate at 6-12 mg/kg completely restored the antitumor activity of paclitaxel, etoposide, and vincristine against two highly resistant MDR human tumor xenograft tumors (2780AD and H69/LX4) in nude mice. It was also shown that in vivo Tariquidar methanesulfonate hydrate significantly potentiated the anticancer effect of doxorubicin against subcutaneous MC26 tumors. [2]