抗叶酸耐药性
中文名称
通路描述
自 20 世纪 40 年代以来，抗叶酸药在恶性肿瘤、微生物、寄生虫和慢性炎症疾病的药物治疗中发挥了关键作用。抗叶酸药的抗增殖活性分子基础依赖于抑制叶酸代谢中的关键酶，导致嘌呤和胸苷酸生物合成中断、DNA 复制受阻和细胞死亡。抗叶酸药的抗炎特性主要与其阻断肿瘤坏死因子（TNF）-α或白细胞介素（IL）-1β等促炎细胞因子的释放有关。细胞对抗叶酸药的耐药性可能源于药物入胞受损、药物外排增强、抗叶酸药通过多聚谷氨酰胺化激活受阻、抗叶酸药多聚谷氨酰胺的水解增加、靶酶表达和突变的增加，以及细胞内四氢叶酸辅因子池的增强。
英文描述
Since the 1940s, antifolates have played a pivotal role in drug treatment of malignant, microbial, parasitic and chronic inflammatory diseases. The molecular basis of the anti-proliferative activity of antifolates relies on inhibition of key enzymes in folate metabolism, which results in disruption of purine and thymidylate biosynthesis, inhibition of DNA replication and cell death. The anti-inflammatory properties of antifolate have been most strongly related to its ability to block the release of pro-inflammatory cytokines such as tumour necrosis factor (TNF)-alpha or interleukin (IL)-1beta. Cells may develop resistance to an antifolate drug by virtue of impaired drug transport into cells, augmented drug export, impaired activation of antifolates through polyglutamylation, augmented hydrolysis of antifolate polyglutamates, increased expression and mutation of target enzymes, and the augmentation of cellular tetrahydrofolate-cofactor pools in cells.
所含基因
30 个基因