Synonym
Azathioprine, US brand name: Imuran. Foreign brand name: Imurel. Abbreviations: AZA. AZTP.
IUPAC/Chemical Name
6-((1-methyl-4-nitro-1H-imidazol-5-yl)thio)-7H-purine
InChi Key
LMEKQMALGUDUQG-UHFFFAOYSA-N
InChi Code
InChI=1S/C9H7N7O2S/c1-15-4-14-7(16(17)18)9(15)19-8-5-6(11-2-10-5)12-3-13-8/h2-4H,1H3,(H,10,11,12,13)
SMILES Code
O=[N+](C1=C(SC2=C3NC=NC3=NC=N2)N(C)C=N1)[O-]
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Azathioprine is used in organ transplantation and autoimmune disease. Some of the autoimmune diseases are rheumatoid arthritis, pemphigus, Inflammatory Bowel Disease (such as Crohn's disease and Ulcerative Colitis), multiple sclerosis, autoimmune hepatitis, atopic dermatitis, Myasthenia Gravis and restrictive lung disease. Azathioprine interferes with the synthesis of purines (adenine and guanine), which is required for DNA synthesis. Fast-growing cells, including T-cells and B-cells, are particularly affected by the inhibition of purine synthesis. It is a pro-drug, converted in the body to the active metabolites 6-mercaptopurine (6-MP) and 6-thioinosinic acid. Azathioprine is produced by a number of generic manufacturers and as branded names (Azasan by Salix in the U.S., Imuran by GlaxoSmithKline in Canada and the U.S., Australia and UK, Azamun in Finland and Imurel in Scandinavia and France).
According to http://en.wikipedia.org/wiki/Azathioprine, Azathioprine was first introduced into clinical practice by Sir Roy Calne, the British pioneer in transplantation. Following the work done by Sir Peter Medawar in discovering the immunological basis of rejection of transplanted tissues and organs, Calne introduced 6-mercaptopurine as an experimental immunosuppressant for kidney transplants cardiac transplantation. When azathioprine was discovered, he then introduced it as a less toxic replacement for 6-mercaptopurine. For many years, dual therapy with azathioprine and steroids was the standard anti-rejection regime, until cyclosporine was introduced into clinical practice (also by Calne) in 1978.
DRUG DESCRIPTION
AZASAN®, an immunosuppressive antimetabolite, is available in tablet form for oral administration. Each scored tablet contains 75 mg or 100 mg azathioprine and the inactive ingredients lactose monohydrate, pregelatinized starch, povidone, corn starch, magnesium stearate, and stearic acid. It is an imidazolyl derivative of 6-mercaptopurine and many of its biological effects are similar to those of the parent compound. Azathioprine is insoluble in water, but may be dissolved with addition of one molar equivalent of alkali. The sodium salt of azathioprine is sufficiently soluble to make a 10 mg/mL water solution which is stable for 24 hours at 59° to 77°F (15° to 25°C). Azathioprine is stable in solution at neutral or acid pH but hydrolysis to mercaptopurine occurs in excess sodium hydroxide (0.1N), especially on warming. Conversion to mercaptopurine also occurs in the presence of sulfhydryl compounds such as cysteine, glutathione, and hydrogen sulfide.
Biological target:
Azathioprine (Azasan, Imuran; BW 57-322) is an immunosuppressive antimetabolite pro-drug.
In vitro activity:
The data presented in this study show that intestinal epithelial restitution is not significantly affected by AZA (Azathioprine), 6-MP or 6-TG at any concentration tested. The here presented data are in accordance with observations in non-epithelial cell populations demonstrating that AZA has no significant effect on migration of oligodendrocyte progenitor cells and endothelial cells in vitro. Epithelial cell proliferation, as another essential mechanism for resealing of mucosal wounds in the intestine, was substantially inhibited by AZA, 6-MP as well as 6-TG. This effect was dose-dependent and maximal at a concentration of 10 μM. Conforming with this observations AZA, 6-MP and 6-TG were found to arrest cell cycle progression in HT-29 cells.
Reference: Regul Pept. 2005 Nov;131(1-3):1-11. https://pubmed.ncbi.nlm.nih.gov/16122821/
In vivo activity:
In the current study, the in vivo long-term effect of AZA (Azathioprine) treatment on mVC in rats was examined. In line with in vitro data, this study shows that AZA treatment over 24 weeks induces vessel calcification and proinflammatory SASP activation in the aortic tissue. The effect is, at least in part, driven by the NLRP3 inflammasome (Figure 6).
Reference: Biomedicines. 2021 Mar; 9(3): 327. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004774/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
36.6 |
131.86 |
| DMF |
12.5 |
45.08 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
277.26
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Al Maruf A, Wan L, O'Brien PJ. Evaluation of azathioprine-induced cytotoxicity in an in vitro rat hepatocyte system. Biomed Res Int. 2014;2014:379748. doi: 10.1155/2014/379748. Epub 2014 Jul 1. PMID: 25101277; PMCID: PMC4101230.
2. Schroll S, Sarlette A, Ahrens K, Manns MP, Göke M. Effects of azathioprine and its metabolites on repair mechanisms of the intestinal epithelium in vitro. Regul Pept. 2005 Nov;131(1-3):1-11. doi: 10.1016/j.regpep.2005.03.001. PMID: 16122821.
3. Schuchardt M, Herrmann J, Henkel C, Babic M, van der Giet M, Tölle M. Long-Term Treatment of Azathioprine in Rats Induces Vessel Mineralization. Biomedicines. 2021 Mar 23;9(3):327. doi: 10.3390/biomedicines9030327. PMID: 33806932; PMCID: PMC8004774.
4. Chalastanis A, Penard-Lacronique V, Svrcek M, Defaweux V, Antoine N, Buhard O, Dumont S, Fabiani B, Renault I, Tubacher E, Fléjou JF, Te Riele H, Duval A, Muleris M. Azathioprine-induced carcinogenesis in mice according to Msh2 genotype. J Natl Cancer Inst. 2010 Nov 17;102(22):1731-40. doi: 10.1093/jnci/djq389. Epub 2010 Oct 5. PMID: 20923998.
In vitro protocol:
1. Al Maruf A, Wan L, O'Brien PJ. Evaluation of azathioprine-induced cytotoxicity in an in vitro rat hepatocyte system. Biomed Res Int. 2014;2014:379748. doi: 10.1155/2014/379748. Epub 2014 Jul 1. PMID: 25101277; PMCID: PMC4101230.
2. Schroll S, Sarlette A, Ahrens K, Manns MP, Göke M. Effects of azathioprine and its metabolites on repair mechanisms of the intestinal epithelium in vitro. Regul Pept. 2005 Nov;131(1-3):1-11. doi: 10.1016/j.regpep.2005.03.001. PMID: 16122821.
In vivo protocol:
1. Schuchardt M, Herrmann J, Henkel C, Babic M, van der Giet M, Tölle M. Long-Term Treatment of Azathioprine in Rats Induces Vessel Mineralization. Biomedicines. 2021 Mar 23;9(3):327. doi: 10.3390/biomedicines9030327. PMID: 33806932; PMCID: PMC8004774.
2. Chalastanis A, Penard-Lacronique V, Svrcek M, Defaweux V, Antoine N, Buhard O, Dumont S, Fabiani B, Renault I, Tubacher E, Fléjou JF, Te Riele H, Duval A, Muleris M. Azathioprine-induced carcinogenesis in mice according to Msh2 genotype. J Natl Cancer Inst. 2010 Nov 17;102(22):1731-40. doi: 10.1093/jnci/djq389. Epub 2010 Oct 5. PMID: 20923998.
1: Gordon M, Taylor K, Akobeng AK, Thomas AG. Azathioprine and 6-mercaptopurine for maintenance of surgically-induced remission in Crohn's disease. Cochrane Database Syst Rev. 2014 Aug 1;8:CD010233. doi: 10.1002/14651858.CD010233.pub2. Review. PubMed PMID: 25081347.
2: Henkenberens C, Franzke A, Raab P, Oschlies I, Klapper W, Christiansen H. Primary EBV-positive Hodgkin's lymphoma of the CNS under azathioprine treatment: case report and review of the literature. Strahlenther Onkol. 2014 Sep;190(9):847-52. doi: 10.1007/s00066-014-0670-9. Epub 2014 May 14. Review. PubMed PMID: 24823896.
3: Maneiro JR, Lopez-Canoa N, Salgado E, Gomez-Reino JJ. Maintenance therapy of lupus nephritis with mycophenolate or azathioprine: systematic review and meta-analysis. Rheumatology (Oxford). 2014 May;53(5):834-8. doi: 10.1093/rheumatology/ket429. Epub 2013 Dec 24. Review. PubMed PMID: 24369416.
4: Dooremont D, Decaestecker J, De Wulf D, Ghillebert G, Van Vlierberghe H, Van Dorpe J, Baert F. Azathioprine induced serious portal hypertension: a case series of three IBD patients and review of the literature. Acta Gastroenterol Belg. 2013 Sep;76(3):342-6. Review. PubMed PMID: 24261031.
5: Mahmood K, Khan AM, Ramanan AV, Martin K. Intentional overdose of azathioprine in a patient with systemic lupus erythematosus. Scott Med J. 2013 Nov;58(4):e3-4. doi: 10.1177/0036933013508040. Review. PubMed PMID: 24215056.
6: Kennedy NA, Rhatigan E, Arnott ID, Noble CL, Shand AG, Satsangi J, Lees CW. A trial of mercaptopurine is a safe strategy in patients with inflammatory bowel disease intolerant to azathioprine: an observational study, systematic review and meta-analysis. Aliment Pharmacol Ther. 2013 Nov;38(10):1255-66. doi: 10.1111/apt.12511. Epub 2013 Oct 5. Review. PubMed PMID: 24117596.
7: Yeter KC, Afkhami M, Brynes RK, Quismorio FP Jr. Aplastic anemia secondary to azathioprine in systemic lupus erythematosus: report of a case with normal thiopurine S-methyltransferase enzyme activity and review of the literature. Lupus. 2013 Dec;22(14):1526-8. doi: 10.1177/0961203313504636. Epub 2013 Sep 12. Review. PubMed PMID: 24029750.
8: Kim MJ, Choe YH. Monitoring and safety of azathioprine therapy in inflammatory bowel disease. Pediatr Gastroenterol Hepatol Nutr. 2013 Jun;16(2):65-70. doi: 10.5223/pghn.2013.16.2.65. Epub 2013 Jun 30. Review. PubMed PMID: 24010109; PubMed Central PMCID: PMC3760698.
9: Koduri PR, Vanajakshi S, Anuradha R. Azathioprine-associated pure red cell aplasia in renal transplant recipients: a report of two cases. Ann Hematol. 2014 Feb;93(2):329-30. doi: 10.1007/s00277-013-1779-0. Epub 2013 May 17. Review. PubMed PMID: 23680868.
10: Chande N, Tsoulis DJ, MacDonald JK. Azathioprine or 6-mercaptopurine for induction of remission in Crohn's disease. Cochrane Database Syst Rev. 2013 Apr 30;4:CD000545. doi: 10.1002/14651858.CD000545.pub4. Review. PubMed PMID: 23633304.
