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Chemistry

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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
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

Arfolitixorin

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


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Arfolitixorin Manufacturers

A Arfolitixorin manufacturer is defined as any person or entity involved in the manufacture, preparation, processing, compounding or propagation of Arfolitixorin, including repackagers and relabelers. The FDA regulates Arfolitixorin manufacturers to ensure that their products comply with relevant laws and regulations and are safe and effective to use. Arfolitixorin API Manufacturers are required to adhere to Good Manufacturing Practices (GMP) to ensure that their products are consistently manufactured to meet established quality criteria.

Arfolitixorin Suppliers

A Arfolitixorin supplier is an individual or a company that provides Arfolitixorin active pharmaceutical ingredient (API) or Arfolitixorin finished formulations upon request. The Arfolitixorin suppliers may include Arfolitixorin API manufacturers, exporters, distributors and traders.

Arfolitixorin GMP

Arfolitixorin Active pharmaceutical ingredient (API) is produced in GMP-certified manufacturing facility.

GMP stands for Good Manufacturing Practices, which is a system used in the pharmaceutical industry to make sure that goods are regularly produced and monitored in accordance with quality standards. The FDA’s current Good Manufacturing Practices requirements are referred to as cGMP or current GMP which indicates that the company follows the most recent GMP specifications. The World Health Organization (WHO) has its own set of GMP guidelines, called the WHO GMP. Different countries can also set their own guidelines for GMP like China (Chinese GMP) or the EU (EU GMP).

PharmaCompass offers a list of Arfolitixorin GMP manufacturers, exporters & distributors, which can be sorted by USDMF, JDMF, KDMF, CEP (COS), WC, API price, and more, enabling you to easily find the right Arfolitixorin GMP manufacturer or Arfolitixorin GMP API supplier for your needs.

Arfolitixorin CoA

A Arfolitixorin CoA (Certificate of Analysis) is a formal document that attests to Arfolitixorin's compliance with Arfolitixorin specifications and serves as a tool for batch-level quality control.

Arfolitixorin CoA mostly includes findings from lab analyses of a specific batch. For each Arfolitixorin CoA document that a company creates, the USFDA specifies specific requirements, such as supplier information, material identification, transportation data, evidence of conformity and signature data.

Arfolitixorin may be tested according to a variety of international standards, such as European Pharmacopoeia (Arfolitixorin EP), Arfolitixorin JP (Japanese Pharmacopeia) and the US Pharmacopoeia (Arfolitixorin USP).

Inform the supplier about your product requirements, specifying if you need a product with particular monograph like EP (Ph. Eur.), USP, JP, BP, or any other quality. In addition, clarify whether you need hydrochloride (HCl), anhydricum, base, micronisatum or a specific level of purity. To find reputable suppliers, utilize the filters and select those certified by GMP, FDA, or any other certification as per your requirement.
For your convenience, we have listed synonyms and CAS numbers to help you find the best supplier. The use of synonyms and CAS numbers can be helpful in identifying potential suppliers, but it is crucial to note that they might not always indicate the exact same product. It is important to confirm the product details with the supplier before making a purchase to ensure that it meets your requirements.
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