Fox Elizabeth, Bates Susan E
National Cancer Institute, Pediatric Oncology Branch, Bethesda, MD 20892, USA.
Expert Rev Anticancer Ther. 2007 Apr;7(4):447-59. doi: 10.1586/14737140.7.4.447.
P-glycoprotein actively transports structurally unrelated compounds out of cells, conferring the multidrug resistance phenotype in cancer. Tariquidar is a potent, specific, noncompetitive inhibitor of P-glycoprotein. Tariquidar inhibits the ATPase activity of P-glycoprotein, suggesting that the modulating effect is derived from the inhibition of substrate binding, inhibition of ATP hydrolysis or both. In clinical trials, tariquidar is tolerable and does not have significant pharmacokinetic interaction with chemotherapy. In patients, inhibition of P-glycoprotein has been demonstrated for 48 h after a single dose of tariquidar. Studies to assess a possible increase in toxicity of chemotherapy and the impact of P-glycoprotein inhibition on tumor response and patient outcome are ongoing. Tariquidar can be considered an ideal agent for testing the role of P-glycoprotein inhibition in cancer.
P-糖蛋白可将结构不相关的化合物主动转运出细胞，从而赋予癌症多药耐药表型。 tariquidar是一种强效、特异性、非竞争性的P-糖蛋白抑制剂。tariquidar可抑制P-糖蛋白的ATP酶活性，这表明其调节作用源于对底物结合的抑制、对ATP水解的抑制或两者兼有。在临床试验中，tariquidar耐受性良好，且与化疗药物不存在显著的药代动力学相互作用。在患者中，单次服用tariquidar后，P-糖蛋白的抑制作用已被证实可持续48小时。评估化疗毒性可能增加以及P-糖蛋白抑制对肿瘤反应和患者预后影响的研究正在进行中。tariquidar可被视为测试P-糖蛋白抑制在癌症中作用的理想药物。
