6-methylmercaptopurine ribonucleotide

Fig. 2 Metabolism of 6-mercaptopurine (6-MP) via xanthine oxidase (XO) to the inactive metabolite 6-thiouric acid (6-TU), thiopurine S-methyltransferase (TPMT) to the inactive metabolite 6-methylmercaptopurine (6-MMP), and hypoxanthine guanine phosphoribosyl transferase (HPRT) to 6-thioinosine monophosphate (6-TIMP) which is then further metabolized to thioguanine nucleotides (6-TGN), 6-methylmercaptopurine ribonucleotides (6-MMPR) or 6-thio-inosine triphosphate (6-thio-ITP), these all being active metabolites...

Complete blood counts should be checked every 4 to 12 weeks in patients receiving the drug. For patients on stable dose and adequate blood counts, the blood may be checked less frequently than the patient at risk for low white count. LFTs need to be checked periodically. Some groups check TPMT levels prior to initiating therapy and monitor erythrocyte 6-thioguanine nucleotide and 6-methylmercaptopurine ribonucleotide levels during therapy. 

Purine and Pyrimidine Analogues - The following comments will center upon work published in 1966 Heidelberger has included earlier work in this area in his recent review. Modifications of 6-mercaptopurine (I) are of continuing interest because of mereaptopurine s activity in human leukemia, and the ultimate development of resistance by the leukemic cells to this drug. 6-methylmercaptopurine riboside (II) is converted to 6-methyImercaptopurine ribonucleotide (III) by a nucleoside kinase. Cells... 

A number of purine nucleotide analogues can mimic the effects of natural purine ribonucleotides on PP-ribose-P amidotransferase and thereby effect feedback inhibition of the entire pathway (69, 60). Such nucleotide analogues may be synthesized by cells from purine bases or nucleosides presented to them. A number of compounds with potent inhibitory properties, such as 6-mercaptopurine, 6-thioguanine, and 6-methylmercaptopurine ribonucleoside, inhibit purine biosynthesis de novo in this way, although it is not known whether this action is responsible for the growth inhibition. 

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