6-Thioguanine: a naked bullet? (Or how pharmacogenomics can make old drugs brand new).

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Abstract
6-Mercaptopurine (6-MP) and its prodrug azathioprine are the standard treatment for maintenance and remission induction of steroid-dependant and or fistulizing Crohn's disease (CD) and probably also refractory ulcerative colitis (UC). They act through inhibition of purine de novo synthesis by incorporation of 6-thioguanine (6-TG) metabolites into DNA. There are, however, limitations to the therapy. A significant number of patients do not respond even after adequate dosing (2–2.5 mg/kg for azathioprine and 1–1.5 mg/kg for 6-MP) and duration (4–6 months). Side effects will occur in 10–15% of patients depending on the dose used. Differences in bioavailability among different agents may occur (1). Some side effects are clearly idiosyncratic in nature, e.g., pancreatitis, fever, and rash, whereas other side effects are known to be dose dependent, including nausea, vomiting, liver toxicity, joint pains, and leucopenia.