Tariquidar

Tariquidar is a potent and selective inhibitor of P-glycoprotein (P-gp) with a K_D value of 5.1nM ^[1]. Tariquidar inhibits the ABC transporter ABCB1 by blocking ATPase activity, with an IC₅₀ value of 223 ± 8nM^[2]. Tariquidar has been widely used in multi-drug resistant cell models to inhibit cell proliferation^[3].

In vitro, Tariquidar treatment (33.34µM) for 2 days significantly inhibited the cell viability of MRC5 cells^[4]. The 0.3µM dose of Tariquidar treatment for 72 hours significantly inhibited the expression of MRP7 protein in HEK/MRP7 cells, without affecting the MRP7 mRNA level, and enhanced the sensitivity of the cells to paclitaxel^[5]. The 2-hour pretreatment with 1.5μM Tariquidar significantly enhanced the killing effect of 1μM doxorubicin on MDA-MB-231 cells^[6].

In vivo, Tariquidar via injecting intraperitoneally at a dose of 13mg/kg every two days for 18 days can enhance the efficacy of Astragaloside IV (ASIV) (20mg/kg/day; i, p.) on experimental autoimmune encephalomyelitis (EAE) mice, manifested as reduced clinical symptoms, decreased incidence rate, less inflammatory infiltration in the central nervous system (CNS), and less demyelination^[7]. Male Sprague Dawley rats received a single intravenous dose of Tariquidar (7.5mg/kg) for 2h inhibited the P-gp efflux of ondansetron in the brain and spinal cord^[8].

References:
[1] Weidner L D, Fung K L, Kannan P, et al. Tariquidar is an inhibitor and not a substrate of human and mouse P-glycoprotein[J]. Drug Metabolism and Disposition, 2016, 44(2): 275-282.
[2] Kühnle M, Egger M, Müller C, et al. Potent and selective inhibitors of breast cancer resistance protein (ABCG2) derived from the p-glycoprotein (ABCB1) modulator tariquidar[J]. J Med Chem, 2009, 52(4): 1190-7.
[3] Mistry P, Stewart A J, Dangerfield W, et al. In vitro and in vivo reversal of P-glycoprotein-mediated multidrug resistance by a novel potent modulator, XR9576[J]. Cancer research, 2001, 61(2): 749-758.
[4] Parsons A J, Cohen T, Schwarz T M, et al. Valspodar limits human cytomegalovirus infection and dissemination[J]. Antiviral research, 2021, 193: 105124.
[5] Sun Y L, Chen J J, Kumar P, et al. Reversal of MRP7 (ABCC10)-mediated multidrug resistance by tariquidar[J]. PloS one, 2013, 8(2): e55576.
[6] Jadhao M, Tsai E M, Yang H C, et al. The long-term DEHP exposure confers multidrug resistance of triple-negative breast cancer cells through ABC transporters and intracellular ROS[J]. Antioxidants, 2021, 10(6): 949.
[7] Zhang W, Liu M, Yang L, et al. P-glycoprotein inhibitor tariquidar potentiates efficacy of astragaloside IV in experimental autoimmune encephalomyelitis mice[J]. Molecules, 2019, 24(3): 561.
[8] Chiang M, Back H, Lee J B, et al. Pharmacokinetic Modeling of the Effect of Tariquidar on Ondansetron Disposition into the Central Nervous System[J]. Pharmaceutical research, 2024, 41(7): 1401-1411.

Tariquidar是一种高效、选择性的P-糖蛋白抑制剂，K_D值为5.1nM^[1]。Tariquidar通过阻断ATP酶活性抑制ABCB1转运蛋白功能，IC₅₀值为223±8nM^[2]。Tariquidar已广泛应用于多药耐药细胞模型中抑制细胞增殖^[3]。

在体外，使用33.34µM的Tariquidar处理MRC5细胞2天可显著抑制细胞活力^[4]。用0.3µM的Tariquidar处理HEK/MRP7细胞72小时，能显著降低MRP7蛋白表达水平且不影响其mRNA，同时增强细胞对紫杉醇的敏感性^[5]。用1.5μM的Tariquidar预处理MDA-MB-231细胞2小时，可显著增强1μM多柔比星对细胞的杀伤效果^[6]。

在体内，每两天腹腔注射13mg/kg剂量的Tariquidar持续18天，能增强Astragaloside IV (ASIV) (20mg/kg/day; i.p.)对实验性自身免疫性脑脊髓炎(EAE)小鼠的治疗效果，表现为临床症状减轻、发病率下降、中枢神经系统炎症浸润及脱髓鞘病变减少^[7]。单次静脉注射7.5mg/kg剂量的Tariquidar 2小时，可抑制在雄性Sprague Dawley大鼠的大脑和脊髓中由P-糖蛋白介导ondansetron外排作用^[8]。