Preferred Label : Arfolitixorin;
NCIt synonyms : [6R] 5,10-methylenetetrahydrofolate; [6R]-5,10-methylene-tetrahydrofolate; 6R-MTHF; 6R-5-10-Methylenetetrahydrofolate; Methylenetetrahydrofolic Acid, L-( )-; (6R)-5,10-Methylenetetrahydrofolate; 6R-5,10-methyleneTHF; 6R-methylene THF;
NCIt definition : 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.;
UNII : Z8R4A37V9Q;
InChIKey : QYNUQALWYRSVHF-OLZOCXBDSA-N;
CAS number : 31690-11-6;
Drug name : Modufolin; Rescufolin;
NCI Metathesaurus CUI : CL936794;
Origin ID : C157079;
UMLS CUI : C4760869;
Semantic type(s)
- concept_is_in_subset
