6-Mercaptopurine cross resistance

A number of derivatives of mercaptopurine have antimetabolite activity, but cell lines with acquired resistance to 6-MP are also cross-resistant to these derivatives, showing that their mechanism of action is essentially similar to 6-MP. Tumours resistant to 6-MP lose their sensitivity to 6-chloropurine (Fig. 9) at the same time. One possible exception is 6-methylmercaptopurine (6-MeMP, Fig. 9) which still affects tumours which have acquir resistance to 6-MP. Resistance to 6-MP is usually a result of the cell losing the pyrophosphate phosphoribosyl transferase, required to convert 6-MP to TIMP. 6-MeMP probably retains its activity because it is converted to its active ribotides by a different series of enzymes. Its ultimate mechanism of action may in fact be on purine biosynthesis similar to 6-MP. 

Mercaptonurine - 5-Formamide-l-B-ribofuranosylthioimidazole-4-carboxamide 2, 3, 5 -triformate, is comparable with 6-mercaptopurine (6-MP) for the treatment of leukemias.33 it is cross-resistant with 6-MP. Conversion of 6-MP ribonucleoside to 6-MeMP ribonucleotide has been shown in L-1210 leukemia cells, adenocarcinoma 755 cells, H. Ep. No. 2 cells and other systems. 6-MeMP ribonucleotide is responsible for the inhibition of purine synthesis produced by 6-MP.3 Metabolism of 6-MeMP in Ehrlich ascites cells has been studied.Breakdown of the active nucleotide form of the 6-thlopurines by alkaline phosphohydrolase is probably responsible... 

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