The Mechanism of Action of 6-mercaptopurine. I. Biochemical Effects.

systems (3—5,12, 13, 17, 18) have led to the hypothesis that the active form of 6-MP is its ribonucleotide (thio inosinate, 6-thio IMP), which inhibits the further conver sion by inosinate to other purine ribonucleotides (4, 5). This inhibition by thioinosinate of the formation of ade nylate and guanylate has been demonstrated in cell-free preparations from Streptococcus faecalis and pigeon liver, respectively (26). In L1210, studies on the incorporation of labeled hypoxanthine into nucleic acid punines are con sistent with the inhibition at the level of hypoxanthine, but only the conversion to adenylate seems to be seriously affected by 6-MP (10). More recent studies with partially purified inosine-5'-phosphate-NAD-oxidoreductase (IMP dehydrogenase) from bacteria (15) and Ehrlich ascites