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    Arfolitixorin

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    2D Structure
    Also known as: Arfolitixorin, 31690-11-6, Modufolin, 6r-mthf, Methylenetetrahydrofolic acid, l-(+)-, Arfolitixorin [usan]
    Molecular Formula
    C20H23N7O6
    Molecular Weight
    457.4  g/mol
    InChI Key
    QYNUQALWYRSVHF-OLZOCXBDSA-N
    FDA UNII
    Z8R4A37V9Q
    Arfolitixorin is 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.
    1 2D Structure

    2D Structure

    2 Identification
    2.1 Computed Descriptors
    2.1.1 IUPAC Name
    (2S)-2-[[4-[(6aR)-3-amino-1-oxo-2,5,6,6a,7,9-hexahydroimidazo[1,5-f]pteridin-8-yl]benzoyl]amino]pentanedioic acid
    2.1.2 InChI
    InChI=1S/C20H23N7O6/c21-20-24-16-15(18(31)25-20)27-9-26(8-12(27)7-22-16)11-3-1-10(2-4-11)17(30)23-13(19(32)33)5-6-14(28)29/h1-4,12-13H,5-9H2,(H,23,30)(H,28,29)(H,32,33)(H4,21,22,24,25,31)/t12-,13+/m1/s1
    2.1.3 InChI Key
    QYNUQALWYRSVHF-OLZOCXBDSA-N
    2.1.4 Canonical SMILES
    C1C2CN(CN2C3=C(N1)N=C(NC3=O)N)C4=CC=C(C=C4)C(=O)NC(CCC(=O)O)C(=O)O
    2.1.5 Isomeric SMILES
    C1[C@@H]2CN(CN2C3=C(N1)N=C(NC3=O)N)C4=CC=C(C=C4)C(=O)N[C@@H](CCC(=O)O)C(=O)O
    2.2 Other Identifiers
    2.2.1 UNII
    Z8R4A37V9Q
    2.3 Synonyms
    2.3.1 MeSH Synonyms

    1. 5,10-methylene-5,6,7,8-tetrahydrofolate

    2. 5,10-methylenetetrahydrofolate

    3. 5,10-methylenetetrahydrofolate Monohydrochloride, (l-glu)-isomer

    4. 5,10-methylenetetrahydrofolate, (d-glu)-isomer

    5. 5,10-methylenetetrahydrofolate, (l-glu)-(s)-isomer

    6. 5,10-methylenetetrahydrofolic Acid

    7. Ch2h4fol

    8. Ch2h4folate

    9. N5,n10-methylene-5,6,7,8-tetrahydrofolic Acid

    10. Tetrahydromethylenefolate

    2.3.2 Depositor-Supplied Synonyms

    1. Arfolitixorin

    2. 31690-11-6

    3. Modufolin

    4. 6r-mthf

    5. Methylenetetrahydrofolic Acid, L-(+)-

    6. Arfolitixorin [usan]

    7. (6r)-5,10-methylenetetrahydrofolic Acid

    8. Chebi:1989

    9. Z8r4a37v9q

    10. Iso-901

    11. L-(+)-methylenetetrahydrofolic Acid

    12. 5,10-methylene-thf

    13. 5,10-methylene-(6r)-tetrahydrofolic Acid

    14. (2s)-2-[[4-[(6ar)-3-amino-1-oxo-4,5,6,6a,7,9-hexahydroimidazo[1,5-f]pteridin-8-yl]benzoyl]amino]pentanedioic Acid

    15. 3432-99-3

    16. 5,10-methylenetetrahydrofolate

    17. N-({4-[(6ar)-3-amino-1-oxo-1,2,5,6,6a,7-hexahydroimidazo[1,5-f]pteridin-8(9h)-yl]phenyl}carbonyl)-l-glutamic Acid

    18. N-{4-[(6ar)-3-amino-1-oxo-1,2,5,6,6a,7-hexahydroimidazo[1,5-f]pteridin-8(9h)-yl]benzoyl}-l-glutamic Acid

    19. Unii-z8r4a37v9q

    20. Arfolitixorin [inn]

    21. Arfolitixorin (usan/inn)

    22. Schembl186747

    23. Arfolitixorin [who-dd]

    24. Chembl1234270

    25. Dtxsid60185584

    26. Bcp09003

    27. Zinc4228243

    28. (6r)-5,10-mthf

    29. Who 10689

    30. Db12676

    31. 5,10-methylene,5,6,7,8-tetrahydrofolate

    32. D11447

    33. D-n5,n10-methylene-l-tetrahydrofolic Acid

    34. Q26995704

    35. (6r,s)-5,10-methylene-5,6,7,8-tetrahydrofolic Acid

    36. [6r]-5,10-methylenetetrahydrofolate ([6r]-5,10- Mthf)

    37. (6r)-5,10-methylene-5,6,7,8-tetrahydrofolic Acid

    38. (2s)-2-[[4-[(6ar)-3-amino-1-oxo-2,5,6,6a,7,9-hexahydroimidazo[1,5-f]pteridin-8-yl]benzoyl]amino]pentanedioic Acid

    39. (s)-2-(4-((r)-3-amino-1-oxo-5,6,6a,7-tetrahydroimidazo[1,5-f]pteridin-8(1h,4h,9h)-yl)benzamido)pentanedioic Acid

    40. (s)-2-(4-((r)-3-amino-1-oxo-5,6,6a,7-tetrahydroimidazo[1,5-f]pteridin-8(1h,4h,9h)-yl)benzamido)pentanedioicacid

    41. L-glutamic Acid, N-(4-((6ar)-3-amino-1,2,5,6,6a,7-hexahydro-1-oxoimidazo(1,5-f)pteridin-8(9h)-yl)benzoyl)-

    42. N-({4-[(6ar)-3-amino-1-oxo-1,4,5,6,6a,7-hexahydroimidazo[1,5-f]pteridin-8(9h)-yl]phenyl}carbonyl)-l-glutamic Acid

    43. N-(4-((6ar)-3-amino-1-oxo-1,2,5,6,6a,7-hexahydroimidazo(1,5-f)pteridin-8(9h)- Yl)benzoyl)-l-glutamic Acid

    2.4 Create Date
    2019-01-15
    3 Chemical and Physical Properties
    Molecular Weight 457.4 g/mol
    Molecular Formula C20H23N7O6
    XLogP3-0.5
    Hydrogen Bond Donor Count6
    Hydrogen Bond Acceptor Count10
    Rotatable Bond Count7
    Exact Mass457.17098148 g/mol
    Monoisotopic Mass457.17098148 g/mol
    Topological Polar Surface Area190 Ų
    Heavy Atom Count33
    Formal Charge0
    Complexity911
    Isotope Atom Count0
    Defined Atom Stereocenter Count2
    Undefined Atom Stereocenter Count0
    Defined Bond Stereocenter Count0
    Undefined Bond Stereocenter Count0
    Covalently Bonded Unit Count1
    4 Drug and Medication Information
    4.1 Drug Indication

    Treatment of colorectal cancer