The efficacy of azathioprine and mercaptopurine is well established in the treatment of active Crohn’s disease and as a long-term maintenance therapy to prevent relapse in both Crohn’s disease and ulcerative colitis.1 Approximately 15% of patients treated with azathioprine or mercaptopurine have adverse reactions. While some of these reactions are dose-dependent, others, including pancreatitis,...

Thioguanine and mercaptopurine are prodrugs requiring conversion into thiopurine nucleotides to exert cytotoxicity. Thiopurine S-methyltransferase (TPMT), an enzyme subject to genetic polymorphism, catabolizes thiopurines into inactive methylated bases, but also produces methylthioguanine nucleotides and methylmercaptopurine nucleotides from thioguanine and mercaptopurine nucleotides, respectiv...

Treatment-related toxicity can be life-threatening and is the primary cause of interruption or discontinuation of chemotherapy for acute lymphoblastic leukemia (ALL), leading to an increased risk of relapse. Mercaptopurine is an essential component of continuation therapy in all ALL treatment protocols worldwide. Genetic polymorphisms in thiopurine S-methyltransferase (TPMT) are known to have a...

MMPR2 is an adenosine analog with substantial antitumor activity in experimental systems (1 , 12). It is not cross resistant with 6-mercaptopurine; Le., it maintains its activity in Ll210 mouse leukemia and human cancer cells in culture, which are resistant to 6-mercaptopurine (2, 4). The biochem ical basis for this lack of cross-resistance has been established (1, 4, 14). Resistance to the thi...

Of 142 purines, purine nucleosides, and analogues tested for inhibition of growth of Escherichia coli B Hill, 45 were active. Of these, 27 were evaluated for inhibition of other E. coli lines, including those resistant to 6-thioguanine, 2-fluoroadenosine, 2,6-diaminopurine, or 6-mercaptopurine. Most toxic to the parent lines were 2-fluoroadenosine, 2-fluoroadenine, 2-fluoro-5'-deoxyadenosine, a...

Background: 6-Mercaptopurine (6-MP), a widely used anti-metabolite for the maintenance phase of childhood acute lymphoblastic leukemia (ALL), has been observed to cause myelotoxicity due genetic polymorphism thiopurine methyl transferase (TPMT), one drug-metabolizing enzymes. This study aimed determine frequency S-methyl (TPMT) polymorphic variants in group Pakistani children with (ALL) using 6...

Studies on the carcinostatic purine analogue, 6-mercaptopurine, have revealed a variety of effects produced by this drug on biochemical reactions (1, 2). The inhibitory action of the drug on any particular biochemical pathway, however, may not be causally related to the inhibition of cell growth, since the drug effect may not be of vital concern to the cell, or a compensatory pathway may become...

1. The transport of 6-thioguanine and 6-mercaptopurine has been studied with isolated jejunal loops of mouse small intestine. H.p.l.c. was used to identify and quantify the thiopurines and their metabolites in the serosal secretions. 2. When the lumen of the intestinal loops contained either 6-thioguanine or 6-mercaptopurine at a concentration of 1 mmol/l, the concentration of unmetabolized dru...

In male BALB/c mice, a combination of individually non-lethal doses of 6-mercaptopurine and endotoxin was significantly lethal. In contrast, mice treated with phenobarbital were resistant to this lethal effect. The high levels of thioinosinic acid in mice that were treated with endotoxin contrasted significantly with the levels in phenobarbital-treated mice. On the other hand, the concentration...

Twenty-two adult patients with acute nonlymphocytic leukemia received daunorubicin, and 21 received a combina tion of prednisone, vincristine, 6-mercaptopurine, and methotrexate in a randomized study. The single agent was superior to the combination in inducing complete remission (50 versus 28%). In addition, patients who completely responded to daunorubicin did so in a median of 19 days, where...