吉西他滨的耐药性及其结构修饰研究进展

Research Progress in Drug Resistance and Structural Modification of Gemcitabine

吉西他滨是FDA批准为一种治疗多种癌症的化疗药物,被广泛应用于治疗各种实体瘤。虽然吉西他滨在临床上成功应用,但其较短的血浆半衰期,向细胞扩散较差,以及不良毒性降低其化疗潜力。吉西他滨的临床表现受到其不满意的药代动力学参数和易失活的严重限制,主要是由于吉西他滨快速脱氨作用,以及活化吉西他滨的脱氧胞苷激酶(DCK)缺乏和核苷转运蛋白的改变等。因此,设计合成吉西他滨的前体药物以提高吉西他滨的治疗效果至关重要。

Gemcitabine is a chemotherapy drug approved by FDA for the treatment of multiple cancers, and is widely used for the treatment of various solid tumors. Although gemcitabine has been successfully used in clinical practice, its short plasma half-life, poor cell diffusion and adverse toxicity reduce its chemotherapy potential. The clinical performance of gemcitabine is severely limited by its unsatis-fied pharmacokinetic parameters and easy inactivation, mainly due to the rapid deamination of gemcitabine, the lack of deoxycytidine kinase (DCK) activated by gemcitabine and the change of nucleoside transporter. Therefore, it is very important to design and synthesize the precursor drugs of gemcitabine to improve the therapeutic effect of gemcitabine.