Xr 9576

Xr 9576 - Names and Identifiers

Name	Tariquidar (methanesulfonate, hydrate)
Synonyms	XR9576 XR-9576 XR 9576 Tariquidar methanesulfonate XR9576 methanesulfonate, hydrate TARIQUIDAR METHANESULFONATE HYDRATE Tariquidar (methanesulfonate, hydrate) Tariquidar (Methanesulfonate, hydrate) Tariquidar dimethanesulfonate hexahydrate Tariquidar methanesulfonate hydrate (XR9576) N-[2-({4-[2-(6,7-Dimethoxy-3,4-dihydro-2(1H)-isoquinolinyl)ethyl]phenyl}carbamoyl)-4,5-dimethoxyphenyl]-3-quinolinecarboxamide
CAS	625375-83-9

Xr 9576 - Physico-chemical Properties

Molecular Formula	C40H52N4O15S2
Molar Mass	892.98868
Solubility	DMSO: ≥ 296 mg/mL; H₂O: < 8.9 mg/mL
Storage Condition	-20℃
In vitro study	Tariquidar methanesulfonate, hydrate (XR9576 methanesulfonate, hydrate) is a potent modulator of P-gp mediated [ 3 H]-Vinblastine and [ 3 H]-Paclitaxel transport as it increases the steady-state accumulation of these cytotoxics in CH r B30 cells to levels observed in non-P-gp-expressing AuxB1 cells (EC 50 =487±50 nM). [ 3 H]-Tariquidar binds to CH r B30 membranes with the highest affinity (K d =5.1±0.9 nM, n=7) and a binding capacity (B max ) of 275±15 pmol/mg membrane protein. In contrast to the parental cell line, the accumulation of [ 3 H]-Vinblastine is increased in a dose-dependent fashion by the modulators XR9576 (EC 50 =487±50 nM). The MDR modulator Tariquidar is able to inhibit 60-70% of the vanadate-sensitive ATPase activity, with potent IC 50 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 [ 3 H]Azidopine implying a direct interaction with the protein.
In vivo study	In mice bearing the intrinsically resistant MC26 colon tumors, coadministration of Tariquidar methanesulfonate, hydrate (XR9576 methanesulfonate, hydrate) 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.