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- NCIT_C157079 IAO_0000115 "The R-isomer of folitixorin, a reduced folate-based biomodulator and active metabolite of folate drugs leucovorin (LV) and levoleucovorin (l-LV) that can be used to increase the efficacy of certain antimetabolites, such as the cytotoxic agent 5-fluorouracil (5-FU), and reduce as well as protect against certain antimetabolite-associated adverse effects, such as those seen with high-dose (HD) methotrexate. Upon administration of arfolitixorin, 5,10-methylenetetrahydrofolate (MTHF) is a reduced folate substrate for the enzyme thymidylate synthase (TS) and stabilizes, upon co-administration of 5-FU, the covalent binding of the 5-FU metabolite 5-fluoro-2'-deoxyuridine-5'-monophosphate (FdUMP), instead of deoxyuridine monophosphate (dUMP), to its target enzyme TS, which results in an inhibition of TS. This inhibits the synthesis of deoxythymidine monophosphate (dTMP) and leads to the depletion of thymidine triphosphate (TTP), which is a necessary constituent of DNA. This inhibits DNA synthesis, which leads to an inhibition of cellular proliferation and induces tumor cell death. As MTHF is able to stabilize and strengthen the ternary complex, co-administration of arfolitixorin enhances the inhibition of DNA synthesis and increases the cytotoxic effect of 5-FU. As MTHF is the active form of folate and the active metabolite of LV and l-LV, arfolitixorin does not need to be converted to an active metabolite to become activated. In DNA synthesis, a ternary complex is formed between the reduced folate substrate MTHF, the TS enzyme and dUMP in order to convert dUMP to the DNA building block dTMP, which is necessary for DNA synthesis." @default.
- NCIT_C157079 NCIT_A32 NCIT_C1909 @default.
- NCIT_C157079 NCIT_NHC0 "C157079" @default.
- NCIT_C157079 NCIT_P106 "Organic Chemical" @default.
- NCIT_C157079 NCIT_P106 "Pharmacologic Substance" @default.
- NCIT_C157079 NCIT_P107 "Arfolitixorin" @default.
- NCIT_C157079 NCIT_P108 "Arfolitixorin" @default.
- NCIT_C157079 NCIT_P208 "CL936794" @default.
- NCIT_C157079 NCIT_P210 "31690-11-6" @default.
- NCIT_C157079 NCIT_P319 "Z8R4A37V9Q" @default.
- NCIT_C157079 NCIT_P322 "CTRP" @default.
- NCIT_C157079 NCIT_P322 "FDA" @default.
- NCIT_C157079 NCIT_P322 "GDC" @default.
- NCIT_C157079 NCIT_P329 "796585" @default.
- NCIT_C157079 NCIT_P330 "796585" @default.
- NCIT_C157079 NCIT_P375 "Arfolitixorin" @default.
- NCIT_C157079 NCIT_P399 "796585" @default.
- NCIT_C157079 normalizedInformationContent "100" @default.
- NCIT_C157079 referenceCount "1" @default.
- NCIT_C157079 hasExactSynonym "(6R)-5,10-Methylenetetrahydrofolate" @default.
- NCIT_C157079 hasExactSynonym "6R-5,10-methyleneTHF" @default.
- NCIT_C157079 hasExactSynonym "6R-5-10-Methylenetetrahydrofolate" @default.
- NCIT_C157079 hasExactSynonym "6R-MTHF" @default.
- NCIT_C157079 hasExactSynonym "6R-methylene THF" @default.
- NCIT_C157079 hasExactSynonym "ARFOLITIXORIN" @default.
- NCIT_C157079 hasExactSynonym "Arfolitixorin" @default.
- NCIT_C157079 hasExactSynonym "Methylenetetrahydrofolic Acid, L-(+)-" @default.
- NCIT_C157079 hasExactSynonym "Modufolin" @default.
- NCIT_C157079 hasExactSynonym "Rescufolin" @default.
- NCIT_C157079 hasExactSynonym "[6R] 5,10-methylenetetrahydrofolate" @default.
- NCIT_C157079 hasExactSynonym "[6R]-5,10-methylene-tetrahydrofolate" @default.
- NCIT_C157079 inSubset NCIT_C116977 @default.
- NCIT_C157079 inSubset NCIT_C116978 @default.
- NCIT_C157079 inSubset NCIT_C128784 @default.
- NCIT_C157079 inSubset NCIT_C157711 @default.
- NCIT_C157079 inSubset NCIT_C157712 @default.
- NCIT_C157079 inSubset NCIT_C176424 @default.
- NCIT_C157079 inSubset NCIT_C177537 @default.
- NCIT_C157079 inSubset NCIT_C63923 @default.
- NCIT_C157079 type Class @default.
- NCIT_C157079 isDefinedBy ncit.owl @default.
- NCIT_C157079 label "Arfolitixorin" @default.
- NCIT_C157079 subClassOf NCIT_C157079 @default.
- NCIT_C157079 subClassOf NCIT_C1908 @default.
- NCIT_C157079 subClassOf NCIT_C1909 @default.
- NCIT_C157079 subClassOf NCIT_C2078 @default.
- NCIT_C157079 subClassOf NCIT_C2140 @default.