The Sound of Evolution
Azathioprine
Mechanism of action:
Azathioprine is metabolized in the body into 6-mercaptopurine, which is then converted by hypoxanthine-guanine phosphoribosyltransferase (HGPRT) into thioinosine monophosphate (TIMP). TIMP can subsequently be metabolized into other molecules such as 6-thioguanosine monophosphate (TGMP), 6-thioguanine triphosphate (TGTP), 6-thio-deoxyguanosine triphosphate (TdGTP), and 6-methylthioinosine monophosphate (MeTIMP).
TIMP and TGMP exert feedback inhibition on amidophosphoribosyltransferase, thereby preventing the synthesis of purine nucleotides such as IMP, AMP, and GMP. In addition, TGTP and TdGTP can be incorporated into RNA and DNA, resulting in abnormal base pairing. These effects suppress the growth of rapidly dividing immune cells and can induce apoptosis.
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.