U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C20H25N7O6
Molecular Weight 459.4558
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LEVOMEFOLIC ACID

SMILES

CN1[C@@H](CNC2=CC=C(C=C2)C(=O)N[C@@H](CCC(O)=O)C(O)=O)CNC3=C1C(=O)NC(N)=N3

InChI

InChIKey=ZNOVTXRBGFNYRX-STQMWFEESA-N
InChI=1S/C20H25N7O6/c1-27-12(9-23-16-15(27)18(31)26-20(21)25-16)8-22-11-4-2-10(3-5-11)17(30)24-13(19(32)33)6-7-14(28)29/h2-5,12-13,22H,6-9H2,1H3,(H,24,30)(H,28,29)(H,32,33)(H4,21,23,25,26,31)/t12-,13-/m0/s1

HIDE SMILES / InChI

Molecular Formula C20H25N7O6
Molecular Weight 459.4558
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

For people with MTHFR gene variations, supplementing with the already activated form of folate (5-MTHF/5- METHYLTETRAHYDROFOLATE/LEVOMEFOLIC ACID) is far more effective in providing this form of folate than introducing the pre-converted form to the body through typical folate supplements. L-Methylfolate (5-MTHF) supplements provide the active form of folate naturally present in the body and available for biological action. 5-MTHF—the “active” form of folate that is able to pass the blood brain barrier. However, without a properly functioning methylenetetrahydrofolate reductase, MTHFR this conversion cannot take place and folate is not converted to forms that can cross the blood brain barrier. That is where 5-MTHF supplements come in. Levomefolate calcium is structurally identical to L-5-methyltetrahydrofolate (L-5-methyl-THF), a metabolite of vitamin B9. Mean baseline concentrations of about 15 nmol/L are reached in populations without folate food fortification under normal nutritional conditions. Orally administered levomefolate calcium is absorbed and is incorporated into the body folate pool. Peak plasma concentrations of about 50 nmol/L above baseline are reached within 0.5 – 1.5 hours after single oral administration of 0.451 mg levomefolate calcium. Steady state conditions for total folate in plasma after intake of 0.451 mg levomefolate calcium. In red blood cells, achievement of steady state is delayed due to the long lifespan of red blood cells of about 120 days. Levomefolate calcium is a part of contraceptive tablets: SAFYRA. Safyral is an estrogen/progestin COC (Combined Oral Contraceptive) containing a folate, indicated for use by women to: prevent pregnancy and raise folate levels in women who choose to use an oral contraceptive for contraception. COCs lower the risk of becoming pregnant primarily by suppressing ovulation. Other possible mechanisms may include cervical mucus changes that inhibit sperm penetration and endometrial changes that reduce the likelihood of implantation.

Approval Year

Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Preventing
SAFYRAL

Approved Use

1.1 Oral Contraceptive: Safyral is indicated for use by women to prevent pregnancy. 1.2 Folate Supplementation Safyral is indicated in women who choose to use an oral contraceptive as their method of contraception, to raise folate levels for the purpose of reducing the risk of a neural tube defect in a pregnancy conceived while taking the product or shortly after discontinuing the product.

Launch Date

2010
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Serum folate levels after UVA exposure: a two-group parallel randomised controlled trial.
2001
Marked suppression of the activity of some, but not all, antifolate compounds by augmentation of folate cofactor pools within tumor cells.
2001 Apr 1
Folate protects against oxidative modification of human LDL.
2001 Dec
Low seminal plasma folate concentrations are associated with low sperm density and count in male smokers and nonsmokers.
2001 Feb
Treatment of hyperhomocysteinemia in hemodialysis patients and renal transplant recipients.
2001 Feb
Folate and chemoprevention of colorectal cancer: Is 5-methyl-tetrahydrofolate an active antiproliferative agent in folate-treated colon-cancer cells?
2001 Jul-Aug
Effect of feeding on circulating micronutrient concentrations in the Burmese python (Python molurus).
2001 Jun
Enzymatic determination of homocysteine in cell extracts.
2001 Mar
Antisense inhibition of methylenetetrahydrofolate reductase reduces survival of methionine-dependent tumour lines.
2002 Jul 15
Determination of 5-methyltetrahydrofolate (13C-labeled and unlabeled) in human plasma and urine by combined liquid chromatography mass spectrometry.
2002 Jun 15
5-methyltetrahydrofolate restores endothelial function in uraemic patients on convective haemodialysis.
2002 May
Effect of low doses of 5-methyltetrahydrofolate and folic acid on plasma homocysteine in healthy subjects with or without the 677C-->T polymorphism of methylenetetrahydrofolate reductase.
2002 Sep
Multiple transcription start sites and alternative splicing in the methylenetetrahydrofolate reductase gene result in two enzyme isoforms.
2002 Sep
Does the interaction between maternal folate intake and the methylenetetrahydrofolate reductase polymorphisms affect the risk of cleft lip with or without cleft palate?
2003 Apr 1
Uptake of 5-methyltetrahydrofolate into PC-3 human prostate cancer cells is carrier-mediated.
2003 Aug
Reduced folate transport to the CNS in female Rett patients.
2003 Aug 26
Dietary prevention of post-angioplasty restenosis. From illusion and disillusion to pragmatism.
2003 Dec
Cobalamin-dependent methionine synthase: probing the role of the axial base in catalysis of methyl transfer between methyltetrahydrofolate and exogenous cob(I)alamin or cob(I)inamide.
2003 Dec 16
Tetrahydrofolate and 5-methyltetrahydrofolate are folates with high antioxidant activity. Identification of the antioxidant pharmacophore.
2003 Dec 18
Affinity extraction combined with stable isotope dilution LC/MS for the determination of 5-methyltetrahydrofolate in human plasma.
2003 Feb 1
Determination of 5-methyltetrahydrofolic acid and folic acid in citrus juices using stable isotope dilution-mass spectrometry.
2003 Feb 26
Transport of 5-formyltetrahydrofolate into primary cultured cerebellar granule cells.
2003 Feb 7
Analysis of the human folate receptor beta gene for an association with neural tube defects.
2003 Jun
A mass spectrometric validated high-performance liquid chromatography procedure for the determination of folates in foods.
2003 Jun 18
Residues 45 and 404 in the murine reduced folate carrier may interact to alter carrier binding and mobility.
2003 Jun 27
Methylenetetrahydrofolate reductase polymorphism in advanced colorectal cancer: a novel genomic predictor of clinical response to fluoropyrimidine-based chemotherapy.
2003 May
Specific and sensitive quantification of folate vitamers in foods by stable isotope dilution assays using high-performance liquid chromatography-tandem mass spectrometry.
2003 May
Characterization of mutations in severe methylenetetrahydrofolate reductase deficiency reveals an FAD-responsive mutation.
2003 May
Model studies on the stability of folic acid and 5-methyltetrahydrofolic acid degradation during thermal treatment in combination with high hydrostatic pressure.
2003 May 21
Folate improves endothelial function in patients with coronary heart disease.
2003 Nov
Thrombophilia and pregnancy.
2003 Nov 14
Regulation of S-adenosylmethionine levels in Saccharomyces cerevisiae.
2003 Oct 31
Cerebrospinal fluid pterins and folates in Aicardi-Goutières syndrome: a new phenotype.
2003 Sep 9
Hyperproliferation of homocysteine-treated colon cancer cells is reversed by folate and 5-methyltetrahydrofolate.
2004 Apr
The C677 mutation in methylene tetrahydrofolate reductase gene: correlation with uric acid and cardiovascular risk factors in elderly Korean men.
2004 Apr
Quantitative evaluation of the drug-drug interactions between methotrexate and nonsteroidal anti-inflammatory drugs in the renal uptake process based on the contribution of organic anion transporters and reduced folate carrier.
2004 Apr
A review of folate receptor alpha cycling and 5-methyltetrahydrofolate accumulation with an emphasis on cell models in vitro.
2004 Apr 29
Determination of folate vitamers in human serum by stable-isotope-dilution tandem mass spectrometry and comparison with radioassay and microbiologic assay.
2004 Feb
Comparative study on pressure and temperature stability of 5-methyltetrahydrofolic acid in model systems and in food products.
2004 Feb 11
Red cell N5-methyltetrahydrofolate concentrations and C677T methylenetetrahydrofolate reductase genotype in patients with stroke.
2004 Jan
Thymidylate synthase and methylenetetrahydrofolate reductase gene polymorphisms: relationships with 5-fluorouracil sensitivity.
2004 Jan 26
Placental folate transport and binding are not impaired in pregnancies complicated by fetal growth restriction.
2004 Jul
Mutations of the MTHFR gene (428C>T and [458G>T+459C>T]) markedly decrease MTHFR enzyme activity.
2004 Jun
Folic acid rescues nitric oxide-induced neural tube closure defects.
2004 Mar
5-Methyltetrahydrofolic acid and folic acid measured in plasma with liquid chromatography tandem mass spectrometry: applications to folate absorption and metabolism.
2004 Mar 15
Homocysteine and reactive oxygen species in metabolic syndrome, type 2 diabetes mellitus, and atheroscleropathy: the pleiotropic effects of folate supplementation.
2004 May 10
The methionine synthase polymorphism D919G alters susceptibility to primary central nervous system lymphoma.
2004 May 17
Methionine metabolism in plants: chloroplasts are autonomous for de novo methionine synthesis and can import S-adenosylmethionine from the cytosol.
2004 May 21
Folic acid-mediated inhibition of serum-induced activation of EGFR promoter in colon cancer cells.
2004 Sep
Betaine rescue of an animal model with methylenetetrahydrofolate reductase deficiency.
2004 Sep 15
Patents

Sample Use Guides

Take one tablet daily by mouth at the same time every day
Route of Administration: Oral
neural stem cells (NSCs) were exposed to folic acid or 5-methyltetrahydrofolate (5-MTHF) (0-200 μmol/L) for 24, 48 or 72 h
Substance Class Chemical
Created
by admin
on Fri Dec 15 16:31:26 GMT 2023
Edited
by admin
on Fri Dec 15 16:31:26 GMT 2023
Record UNII
8S95DH25XC
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
LEVOMEFOLIC ACID
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
N-(4-((((6S)-2-AMINO-5-METHYL-4-OXO-1,4,5,6,7,8-HEXAHYDROPTERIDIN-6- YL)METHYL)AMINO)BENZOYL)-L-GLUTAMIC ACID
Systematic Name English
L-5-MTHF
Common Name English
(6S)-5-methyltetrahydrofolate [WHO-DD]
Common Name English
(6S)-5-METHYLTETRAHYDROFOLATE
WHO-DD  
Common Name English
L-METHYLFOLATE
VANDF  
Common Name English
5- METHYLTETRAHYDROFOLATE
Common Name English
5-METHYL-(6S)-TETRAHYDROFOLIC ACID
Common Name English
LEVOMEFOLATE
VANDF  
Common Name English
Levomefolic acid [WHO-DD]
Common Name English
levomefolic acid [INN]
Common Name English
LEVOMEFOLATE [VANDF]
Common Name English
5-MTHF
Common Name English
LEVOMEFOLINIC ACID
Common Name English
L-METHYLFOLATE [VANDF]
Common Name English
LMSR
Common Name English
L-GLUTAMIC ACID, N-(4-((((6S)-2-AMINO-3,4,5,6,7,8-HEXAHYDRO-5-METHYL-4-OXO-6- PTERIDINYL)METHYL)AMINO)BENZOYL)-
Common Name English
LEVOMEFOLIC ACID [USAN]
Common Name English
Code System Code Type Description
FDA UNII
8S95DH25XC
Created by admin on Fri Dec 15 16:31:26 GMT 2023 , Edited by admin on Fri Dec 15 16:31:26 GMT 2023
PRIMARY
DRUG CENTRAL
4621
Created by admin on Fri Dec 15 16:31:26 GMT 2023 , Edited by admin on Fri Dec 15 16:31:26 GMT 2023
PRIMARY
WIKIPEDIA
LEVOMEFOLIC ACID
Created by admin on Fri Dec 15 16:31:26 GMT 2023 , Edited by admin on Fri Dec 15 16:31:26 GMT 2023
PRIMARY
PUBCHEM
135398561
Created by admin on Fri Dec 15 16:31:26 GMT 2023 , Edited by admin on Fri Dec 15 16:31:26 GMT 2023
PRIMARY
CAS
31690-09-2
Created by admin on Fri Dec 15 16:31:26 GMT 2023 , Edited by admin on Fri Dec 15 16:31:26 GMT 2023
PRIMARY
INN
8917
Created by admin on Fri Dec 15 16:31:26 GMT 2023 , Edited by admin on Fri Dec 15 16:31:26 GMT 2023
PRIMARY
DAILYMED
8S95DH25XC
Created by admin on Fri Dec 15 16:31:26 GMT 2023 , Edited by admin on Fri Dec 15 16:31:26 GMT 2023
PRIMARY
NCI_THESAURUS
C81119
Created by admin on Fri Dec 15 16:31:26 GMT 2023 , Edited by admin on Fri Dec 15 16:31:26 GMT 2023
PRIMARY
SMS_ID
100000127631
Created by admin on Fri Dec 15 16:31:26 GMT 2023 , Edited by admin on Fri Dec 15 16:31:26 GMT 2023
PRIMARY
DRUG BANK
DB11256
Created by admin on Fri Dec 15 16:31:26 GMT 2023 , Edited by admin on Fri Dec 15 16:31:26 GMT 2023
PRIMARY
EVMPD
SUB33688
Created by admin on Fri Dec 15 16:31:26 GMT 2023 , Edited by admin on Fri Dec 15 16:31:26 GMT 2023
PRIMARY
RXCUI
1025342
Created by admin on Fri Dec 15 16:31:26 GMT 2023 , Edited by admin on Fri Dec 15 16:31:26 GMT 2023
PRIMARY
CHEBI
18608
Created by admin on Fri Dec 15 16:31:26 GMT 2023 , Edited by admin on Fri Dec 15 16:31:26 GMT 2023
PRIMARY
EPA CompTox
DTXSID00185583
Created by admin on Fri Dec 15 16:31:26 GMT 2023 , Edited by admin on Fri Dec 15 16:31:26 GMT 2023
PRIMARY
RXCUI
1592257
Created by admin on Fri Dec 15 16:31:26 GMT 2023 , Edited by admin on Fri Dec 15 16:31:26 GMT 2023
ALTERNATIVE
NCI_THESAURUS
C1505
Created by admin on Fri Dec 15 16:31:26 GMT 2023 , Edited by admin on Fri Dec 15 16:31:26 GMT 2023
CONCEPT Dietary Supplement
USAN
TT-129
Created by admin on Fri Dec 15 16:31:26 GMT 2023 , Edited by admin on Fri Dec 15 16:31:26 GMT 2023
PRIMARY
ChEMBL
CHEMBL1231574
Created by admin on Fri Dec 15 16:31:26 GMT 2023 , Edited by admin on Fri Dec 15 16:31:26 GMT 2023
PRIMARY
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Levomefolate calcium is structurally identical to L-5-methyltetrahydrofolate (L-5-methyl-THF), a metabolite of vitamin B9
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ACTIVE MOIETY