title: The IMP dehydrogenase inhibitor mycophenolic acid antagonizes the CTP synthetase inhibitor 3-deazauridine in MOLT-3 human leukemia cells: a central role for phosphoribosyl pyrophosphate.
abstract: Mycophenolic acid, an inhibitor of the enzyme IMP dehydrogenase, antagonizes the CTP synthetase inhibitor 3-deazauridine in its anti-proliferative effects on MOLT-3 human T leukemia cells. No depletion of CTP occurred, and decreased amounts of 3-deazuridine-triphosphate were measured in cells incubated with mycophenolic acid and 3-deazuridine. Most probably, these phenomena are related to the increased amounts of PRPP observed, which can result in an increased pyrimidine biosynthesis de novo and, as a consequence, a decreased metabolism of 3-deazauridine via the salvage pathway.
authors.affiliation: Academic Medical Center, University of Amsterdam, Department of Pediatrics, The Netherlands.
authors.forename: A A
authors.initials: AA
authors.lastname: van Berg
authors.forename: P A
authors.initials: PA
authors.lastname: Mooyer
authors.forename: H
authors.initials: H
authors.lastname: van Lenthe
authors.forename: E H
authors.initials: EH
authors.lastname: Stet
authors.forename: R A
authors.initials: RA
authors.lastname: De Abreu
authors.forename: A B
authors.initials: AB
authors.lastname: van Kuilenburg
authors.forename: A H
authors.initials: AH
authors.lastname: van Gennip
mesh_terms: D015092:3-Deazauridine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D019731:Carbon-Nitrogen Ligases; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors*; D007938:Leukemia; D008025:Ligases / Q000037:antagonists & inhibitors*; D009173:Mycophenolic Acid / Q000494:pharmacology*; D010754:Phosphoribosyl Pyrophosphate / Q000378:metabolism*; D012265:Ribonucleotides / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
chemical_list: D004791:Enzyme Inhibitors; D012265:Ribonucleotides; D015092:3-Deazauridine; D010754:Phosphoribosyl Pyrophosphate; D007168:IMP Dehydrogenase; D008025:Ligases; D019731:Carbon-Nitrogen Ligases; C019951:CTP synthetase; D009173:Mycophenolic Acid