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6-mercaptopurine + allopurinol

Development stage: Unknown
Modality: Small Molecules
Administration: Oral

Overview

A combination therapy consisting of low-dose 6-mercaptopurine (6-MP) and allopurinol. This combination alters 6-MP metabolism to favor production of the active metabolite 6-thioguanine nucleotide (6-TGN) while reducing production of the hepatotoxic metabolite 6-methylmercaptopurine (6-MMP). Allopurinol inhibits xanthine oxidase, which normally metabolizes 6-MP to thiouric acid, and indirectly inhibits thiopurine methyltransferase (TPMT) activity. This combination is used to optimize therapy in patients with skewed 6-MP metabolism, particularly in acute lymphoblastic leukemia (ALL) maintenance therapy and inflammatory bowel disease (IBD) treatment.

Targets

TPMT (Thiopurine S-methyltransferase)XO (Xanthine Oxidoreductase)HPRT1 (Hypoxanthine-guanine phosphoribosyltransferase)

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