TARIQUIDAR 二甲磺酸盐六水合物
中文名称:
TARIQUIDAR 二甲磺酸盐六水合物
中文同义词:
TARIQUIDAR 二甲磺酸盐六水合物;P-糖蛋白抑制剂;他立喹达二甲磺酸盐六水合物
英文名称:
XR9576
英文同义词:
XR 9576;XR-9576;XR9576;TARIQUIDAR METHANESULFONATE HYDRATE;XR 9576;XR-9576;N-[2-({4-[2-(6,7-Dimethoxy-3,4-dihydro-2(1H)-isoquinolinyl)ethyl]phenyl}carbamoyl)-4,5-dimethoxyphenyl]-3-quinolinecarboxamide;Tariquidar (Methanesulfonate, hydrate);Tariquidar dimethanesulfonate hexahydrate;XR9576 methanesulfonate, hydrate
CAS号:
625375-83-9
分子式:
C40H52N4O15S2
分子量:
892.98868
EINECS号:
相关类别:
细胞生物学试剂
Mol文件:
625375-83-9.mol
生物活性
Tariquidar methanesulfonate, hydrate (XR9576 methanesulfonate, hydrate) 是有效和特异性的 P-glycoprotein (P-gp) 抑制剂，Kd值为5.1 nM。
靶点
Kd: 5.1 nM (P-gp)
体外研究
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.
体内研究
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.
