Tariquidar  (Synonyms: XR9576)

Tariquidar (XR9576) is a potent and specific inhibitor of P-glycoprotein (P-gp) with the high affinity (K_d=5.1 nM)^[1].

Kd: 5.1 nM (P-gp)^[1]

Tariquidar (XR9576) 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 CH^rB30 cells to levels observed in non-P-gp-expressing AuxB1 cells (EC₅₀=487±50 nM). [³H]-Tariquidar binds to CH^rB30 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 [³H]-Vinblastine is increased in a dose-dependent fashion by the modulators Tariquidar (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^[1]. 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 XR9576. Tariquidar is a potent inhibitor of photoaffinity labeling of P-gp by [³H]Azidopine implying a direct interaction with the protein^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In mice bearing the intrinsically resistant MC26 colon tumors, coadministration of Tariquidar (XR9576) 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^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

646.73

C₃₈H₃₈N₄O₆

206873-63-4

Solid

Off-white to yellow

O=C(C1=CC2=CC=CC=C2N=C1)NC3=CC(OC)=C(OC)C=C3C(NC4=CC=C(CCN5CC6=C(C=C(OC)C(OC)=C6)CC5)C=C4)=O

Room temperature in continental US; may vary elsewhere.

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

• [1]. Martin C, et al. The molecular interaction of the high affinity reversal agent XR9576 with P-glycoprotein. Br J Pharmacol, 1999, 128(2), 403-411.  [Content Brief]

  [2]. Mistry P, et al. In vitro and in vivo reversal of P-glycoprotein-mediated multidrug resistance by a novel potent modulator, XR9576. Cancer Res, 2001, 61(2), 749-758.  [Content Brief]

  [3]. Zimmermann ES, et al. Simultaneous Semimechanistic Population Analyses of Levofloxacin in Plasma, Lung, and Prostate To Describe the Influence of Efflux Transporters on Drug Distribution following Intravenous and Intratracheal Administration. Antimicrob Agents Chemother. 2015 Nov 30;60(2):946-54.  [Content Brief]

  [4]. Kao YH, et al. Regulation of P-glycoprotein expression in brain capillaries in Huntington's disease and its impact on brain availability of antipsychotic agents risperidone and paliperidone. J Cereb Blood Flow Metab. 2016 Aug;36(8):1412-23.  [Content Brief]

  [5]. Matzneller P, et al. Pharmacokinetics of the P-gp Inhibitor Tariquidar in Rats After Intravenous, Oral, and Intraperitoneal Administration. Eur J Drug Metab Pharmacokinet. 2018 Apr 3.  [Content Brief]