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Pathway Description
Azathioprine Action Pathway (New)
Homo sapiens
Drug Action Pathway
Azathioprine is an immunosuppressor prodrug. It is used to treat rheumatoid arthritis, Crohn's disease, and ulcerative colitis. Also, azathioprine is used in the prevention of renal transplant rejection. This molecule is the prodrug of 6-mercaptopurine, also known as mercaptopurine, it is metabolized nonenzymatically by glutathione. Mercaptopurine is also a medication and an immunosuppressor. Azathioprine was synthesized in 1956 to produce a 6-mercaptopurine derivative with a better therapeutic index. The main activity of the drug is to induce cell apoptosis through the modulation of the ras-related C3 botulinum toxin substrate 1 (Rac1) in the B and T cells. Specifically, the 6-thioguanine triphosphate, one metabolite of azathioprine, modulates the activity of Rac1. Additionally, the molecule is thought to cause the inhibition of the synthesis of purine as well as to incorporate itself (6-thioguanine metabolite) in the DNA. Azathioprine is administered both as an oral tablet and as an intravenous injection.
References
Azathioprine Pathway (New) References
Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M: DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. doi: 10.1093/nar/gkx1037.
Pubmed: 29126136
Anstey A, Lear JT: Azathioprine: clinical pharmacology and current indications in autoimmune disorders. BioDrugs. 1998 Jan;9(1):33-47. doi: 10.2165/00063030-199809010-00004.
Pubmed: 18020555
Tiede I, Fritz G, Strand S, Poppe D, Dvorsky R, Strand D, Lehr HA, Wirtz S, Becker C, Atreya R, Mudter J, Hildner K, Bartsch B, Holtmann M, Blumberg R, Walczak H, Iven H, Galle PR, Ahmadian MR, Neurath MF: CD28-dependent Rac1 activation is the molecular target of azathioprine in primary human CD4+ T lymphocytes. J Clin Invest. 2003 Apr;111(8):1133-45. doi: 10.1172/JCI16432.
Pubmed: 12697733
Pelin M, Genova E, Fusco L, Marisat M, Hofmann U, Favretto D, Lucafo M, Taddio A, Martelossi S, Ventura A, Stocco G, Schwab M, Decorti G: Pharmacokinetics and pharmacodynamics of thiopurines in an in vitro model of human hepatocytes: Insights from an innovative mass spectrometry assay. Chem Biol Interact. 2017 Sep 25;275:189-195. doi: 10.1016/j.cbi.2017.08.009. Epub 2017 Aug 12.
Pubmed: 28811125
Elion GB: The purine path to chemotherapy. Science. 1989 Apr 7;244(4900):41-7. doi: 10.1126/science.2649979.
Pubmed: 2649979
Bradford K, Shih DQ: Optimizing 6-mercaptopurine and azathioprine therapy in the management of inflammatory bowel disease. World J Gastroenterol. 2011 Oct 7;17(37):4166-73. doi: 10.3748/wjg.v17.i37.4166.
Pubmed: 22072847
Nevins TE, Thomas W: Quantitative patterns of azathioprine adherence after renal transplantation. Transplantation. 2009 Mar 15;87(5):711-8. doi: 10.1097/TP.0b013e318195c3d5.
Pubmed: 19295316
Zochowska D, Zegarska J, Hryniewiecka E, Samborowska E, Jazwiec R, Tszyrsznic W, Borowiec A, Dadlez M, Paczek L: Determination of Concentrations of Azathioprine Metabolites 6-Thioguanine and 6-Methylmercaptopurine in Whole Blood With the Use of Liquid Chromatography Combined With Mass Spectrometry. Transplant Proc. 2016 Jun;48(5):1836-9. doi: 10.1016/j.transproceed.2016.01.084.
Pubmed: 27496503
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