Disease relevance of Thiopurine S-methylether

• The growth-inhibitory effect of 6-methylmercaptopurine riboside (MMPR) against leukemia L1210 cells in culture was dramatically potentiated by the addition of guanine nucleosides to the medium [1].
• Comparison of the effects of 6- thio- and 6-methylthiopurine ribonucleoside cyclic monophosphates withtheir corresponding nucleosides on the growth of rat hepatoma cells [2].
• Second, a bioassay was conducted in which the toxicity of 6-methylmercaptopurine riboside toward human CEM lymphoblasts was reversed by varying concentrations of the compounds [3].
• The metabolism of azathioprine (AZA) was studied by monitoring the concentrations of red blood cell (RBC) 6-thioguanine nucleotides (6-TGN) and of 6-methylmercaptopurine metabolites (6-mMP) in 27 renal transplantation recipients and in 10 patient subjects with glomerulonephritis (GN) [4].
• Intracellular concentrations of 6-mercaptopurine metabolites, i.e. of 6-thioguanine nucleotides (6-TGN) and of 6-methylmercaptopurine metabolites (6-mMP) were analysed in red blood cells (RBC) of 19 children with acute lymphoblastic leukemia (ALL), the subjects of a maintenance chemotherapy of their first remission [5].

High impact information on Thiopurine S-methylether

• To assess the possibility that selected purine analogues may affect tumor neovascularization, 6-methylmercaptopurine riboside (6-MMPR), 6-methylmercaptopurine, 2-aminopurine, and adenosine were evaluated for the capacity to inhibit angiogenesis in vitro and in vivo [6].
• The Km values for 6-methylmercaptopurine riboside and 5-iodotubercidin, substrates for adenosine kinase, are estimated to be 4.5 microM and 2.6 nM, respectively [7].
• 6-Methylmercaptopurine riboside is a potent and selective inhibitor of nerve growth factor-activated protein kinase N [8].
• Thiopurine metabolites (6-thioguaninenucleotides (6-TGN) and 6-methylmercaptopurine (6-MMP)) were measured in the red blood cells (RBC) of mother and infant directly after delivery [9].
• Cytotoxicity of 6-mercaptopurine (6MP) and 6-methylmercaptopurine ribonucleoside (Me-MPR) was studied in Molt F4 human malignant lymphoblasts [10].

Chemical compound and disease context of Thiopurine S-methylether

• Apparently, 6-methylmercaptopurine ribonucleotides metabolites can cause pancytopenia, as was already known for 6-thioguanine nucleotides [11].

Biological context of Thiopurine S-methylether

• The crystal and molecular structures of 6-methylmercaptopurine trihydrate and of azathioprine dihydrate were determined by the use of three-dimensional, X-ray, diffractometer data and were refined by least squares [12].
• To determine the frequency distribution of TPMT activity in 157 Japanese subjects with different TPMT genotypes, ie, TPMT*1/*1 and TPMT*1/*3, the authors measured levels of 6-methylmercaptopurine formed from 6-mercaptopurine in red blood cells lysates by HPLC [13].
• Relationship between phosphorylation and cytotoxicity of 2-chloroadenosine and 6-methylmercaptopurine riboside in human cells [14].

Anatomical context of Thiopurine S-methylether

• Mean 6-methylmercaptopurine ribonucleotide levels were 1422, 2149 and 1503 pmol/8 x 10(8) red blood cell respectively [15].
• The ED2 cell line was resistant to pyrazofurin and 6-methylmercaptopurine riboside and to araA/EHNA but not to 2-CldAdo or 2-Cl-2'-FaraA [16].
• 6-Methylmercaptopurine riboside resistance in human lymphocytes in the in vivo somatic cell mutation test [17].

Associations of Thiopurine S-methylether with other chemical compounds

• RESULTS: After initiating allopurinol, 6-tioguanine levels increased from a mean of 185.73 +/- 17.7 to 385.4 +/- 41.5 pmol/8 x 10(8) red blood cells (P < 0.001), while 6-methylmercaptopurine decreased from a mean of 10 380 +/- 1245 to 1732 +/- 502 pmol/8 x 10(8) RBCs (P < 0.001) [18].
• Methotrexate increases red blood cell concentrations of 6-methylmercaptopurine ribonucleotide in rats in vivo [19].
• Taken together the results suggest that (a) the kinetic mechanism of adenosine kinase is sequential Bi-Bi, (b) AMP and ADP may regulate enzyme activity in vivo and (c) tubercidin and 6-methylmercaptopurine riboside are monophosphorylated by the parasite enzyme [20].
• These three cell lines were more sensitive to L-alanosine, a potent inhibitor of de novo AMP synthesis, and to an inhibitor of de novo purine nucleotide synthesis, 6-methylmercaptopurine riboside (MMPR) [21].
• For the majority of patients receiving a 1 g/m2 MP intravenous infusion, MP and all metabolites except 6-thioguanine and 6-methylmercaptopurine riboside were present [22].

Gene context of Thiopurine S-methylether

• ESR of sulfur-substituted purines. 6-methylmercaptopurine at 300 K [23].
• In comparison to wild type cells, PFr cells were 100-fold resistant to 6-methylmercaptopurine riboside, suggesting a lack of adenosine kinase activity [24].
• It must be noted that transient increase in 6-methylmercaptopurine levels (6-MMP), a putative toxic metabolite (up to 21.7 nmol/8 x 10(8) RBC), was more frequently observed in the non-SLE group (P < 0.01) [25].

Analytical, diagnostic and therapeutic context of Thiopurine S-methylether

• This method is based on the measurement of the reaction product 6-methylmercaptopurine (6-MMP) by high-performance liquid chromatography (HPLC) [26].

References