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Azathioprine

硫唑嘌呤

Mechanism of action:

Azathioprine 在體內會被代謝成巰嘌呤(6-mercaptopurine),之後再被次黃嘌呤-鳥嘌呤磷酸核苷轉移酶(HGPRT,hypoxanthine-guanine phosphoribosyltransferase)轉化為硫代肌苷單磷酸(TIMP,thioinosine monophosphate),TIMP 之後還可以代謝成其他如 6-thioguanosine monophosphate (TGMP)、6-thioguanine triphosphate(TGTP)、6-thio-deoxyguanosine triphosphate(TdGTP)、6-methylthioinosine monophosphate(MeTIMP)等分子。TIMP 與 TGMP 會回饋性抑制醯胺基磷酸核醣苷基轉移酶(amidophosphoribosyltransferase),導致 IMP、AMP、GMP 等嘌呤核苷酸無法生成。TGTP 與 TdGTP 甚至會摻入 RNA 與 DNA 形成錯誤鹼基對。這些情形會使快速分裂的免疫細胞發生生長受抑制並誘導細胞凋亡。

​Reference(s):

1. Sochacka J et al. (2014). Docking of thiopurine derivatives to human serum albumin and binding site analysis with Molegro Virtual Docker. Acta Pol Pharm. 


2. Van Os EC et al. (1996). Azathioprine pharmacokinetics after intravenous, oral, delayed release oral and rectal foam administration. Gut. 


3. Anstey A et al. (1998). Azathioprine: clinical pharmacology and current indications in autoimmune disorders. BioDrugs.

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