JNJ-7706621 of thiopurine methyltransferase IMP T

NA damage.13 The sulfur atom is methylated by S pr Ugetieren sentieren in the JNJ-7706621 tissue of S And methylmercaptopurine riboside monophosphate is also an important metabolite in the cells. This metabolite is a potent inhibitor of PRPP amidotransferase, the first enzyme of the de novo purine biosynthesis, and its inhibition leads to a reduced purine nucleotide pools. Therefore, there are two prime Re biochemical actions that contribute to the antitumor activity of t by MP, the inhibition of de novo purine synthesis and its incorporation into the DNA of 6 thio 2 deoxyguanosine. No nucleotide analogues of adenine formed MP in the cells, since T IMP is not a substrate for adenylosuccinate synthetase, the first enzyme in the formation of adenine nucleotides from IMP.
Even if it is a substrate for this enzyme, the mechanism of action of this enzyme would remove sulfur 6 and replace it with an asparagine Acid to form S Adenylosuccinic acid, which is the natural product Triciribine of this reaction. A small amount of ITP in T-cells are formed, but this metabolite was not of particular importance for the mechanism of the activity t of the MP. The metabolism of thioguanine is much simpler than that of MP. TG is also a substrate for hypoxanthine / guanine nucleotide concentrations and high TG accumulate in cells treated with TG. T GMP is methylated by S-methyltransferase, but the reaction product, methyl t-GMP, is a potent inhibitor of PRPP amidotransferase.
Therefore, the inhibition of de novo purine biosynthesis is less important to be particularly important for the effect of TG, and the mechanism of cytotoxicity t of TG incorporated into the DNA and subsequently the DNA damage.13 thioguanine for use in myeloid leukemia mie approved acute . Patients, methylation of the purine bases, MP, and TG, which is of thiopurine S a major mechanism of detoxification of these agents.16, 17 The reaction products, methylmercaptopurine S6 and S6 methyl thioguanine, not substrates for hypoxanthine / guanine phosphoribosyl transferase and are therefore not toxic to human cells. About 0.3% of Bev Lkerung does not express functional TPMT activity t, and k entering the treatment these people Can have serious toxicity of thiopurine dinner T be. 2.2. Fluoropyrimidines 2.2.1. 5-Fluorouracil Fluorouracil is an early example of an anti-cancer drug that has con U on the biochemical basis of available information.
It is known that fluorine in the size E Similar to a hydrogen atom, was a fluoro-carbon bond much st Amplifier was as hydrogen bonding of carbon atoms, replacing the reaction mechanism of thymidylate synthase to hydrogen of 5 deoxyuridine with methyl-Parker Page 4 Chem Rev Author manuscript, increases available in PMC 2010 1 July. PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript NIH group of thymidylate and methylenetetrahydrofolate get rat hepatoma cells but not normal liver cells, k Nnten uracil. Using this information and his colleagues assumed that Heidelberger18 Fura would selectively Abbot Maintenance of tumor cells due to their selective metabolism in tumor cells to F dUMP, thymidylate synthetase inhibits the basis of the Unf Remove ability of the enzyme for the fluoro-5. A big part of the first hypothesis it was shown that, although 19 and fura