Tariquidar methanesulfonate hydrate

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

一种有效的特异性 P-gp 抑制剂，Kd 为 5.1 nM。

A potent, specific P-gp inhibitor with Kd of 5.1 nM; potentiates the cytotoxicity of several drugs including doxorubicin, paclitaxel, etoposide, and vincristine in a panel of human MDR cell lines at 25-80 nM; exhibits potent i.v. and p.o. activity without apparently enhancing the plasma pharmacokinetics of paclitaxel or the toxicity of coadministered drugs.Breast Cancer Phase 2 Discontinued.

Tariquidar methanesulfonate, hydrate (XR9576 methanesulfonate, hydrate) is a potent modulator of P-gp mediated [3H]-Vinblastine 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 (EC50=487±50 nM). [3H]-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 [3H]-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 [3H]Azidopine implying a direct interaction with the protein.

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.

XR 9576 | XR-9576 | XR9576

Membrane Transporter/Ion Channel

P-glycoprotein

P-glycoprotein

Cancer

Breast Cancer

625375-83-9

892.9887

C40H52N4O15S2

>98% (HPLC)

DMSO: ≥ 296 mg/mL; H2O: < 8.9 mg/mL

COC1=C(C=C2CN(CCC2=C1)CCC3=CC=C(C=C3)NC(=O)C4=CC(=C(C=C4NC(=O)C5=CC6=CC=CC=C6N=C5)OC)OC)OC.CS(=O)(=O)O.CS(=O)(=O)O.O.O.O

3-Quinolinecarboxamide, N-[2-[[[4-[2-(3,4-dihydro-6,7-dimethoxy-2(1H)-isoquinolinyl)ethyl]phenyl]amino]carbonyl]-4,5-dimethoxyphenyl]-, methanesulfonate, hydrate (1:2:3)

(-20℃)

With Ice Pack

≥ 2 years