Pteroyl-D-glutamic acid (T3D2849)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (1)XML
Targets (1)
Record Information
Version2.0
Creation Date2009-07-21 20:27:20 UTC
Update Date2014-12-24 20:25:52 UTC
Accession NumberT3D2849
Identification
Common NamePteroyl-D-glutamic acid
ClassSmall Molecule
DescriptionThe active metabolite of Folic acid, Pteroyl-D-glutamic acid is used principally as its calcium salt as an antidote to folic acid antagonists which block the conversion of folic acid to folinic acid. Folic acid, a water-soluble B-complex vitamin, is found in foods such as liver, kidneys, yeast, and leafy, green vegetables. Folic acid is used to diagnose folate deficiency and to treat topical sprue and megaloblastic and macrocytic anemias, hematologic complications resulting from a deficiency in folic acid. A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses (poaceae). Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia.
Compound Type
  • Amide
  • Amine
  • Anti-Anemic Agent
  • Antidote
  • Antineoplastic, Adjunct
  • Drug
  • Ester
  • Food Toxin
  • Metabolite
  • Natural Compound
  • Organic Compound
  • Plant Toxin
  • Vitamin
  • Vitamin B Complex
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
(6S)-5-Formyl-5,6,7,8-tetrahydrofolic acid
(6S)-Folinic acid
(6S)-Leucovorin
(S)-Leucovorin
Antianemia factor
Apo-folic
Citrovorum factor
Folinic acid
Fusilev
L-Folinic acid
L-leucovorin
Leucovorin
Levofolene
Levofolinic acid
Levoleucovorin
Mission prenatal
Mittafol
MVC plus
N-Pteroyl-D-glutamic acid
N-[4-({[(6S)-2-amino-5-formyl-4-oxo-1,4,5,6,7,8-hexahydropteridin-6-yl]methyl}amino)benzoyl]-L-glutamic acid
N-[4-[[(2-Amino-5-formyl-1,4,5,6,7,8-hexahydro-4-oxo-6-pteridinyl)methyl]amino]benzoyl]-D-Glutamic acid
Nifolin
Novo-folacid
Novofolacid
Pteroyl-D-glutamate
Pteroylmonoglutamate
Uzel
Vitamin B11
Vitaped
Wellcovorin
Chemical FormulaC20H23N7O7
Average Molecular Mass473.439 g/mol
Monoisotopic Mass473.166 g/mol
CAS Registry Number1492-18-8
IUPAC Name(2S)-2-{[4-({[(6S)-2-amino-5-formyl-4-oxo-1,4,5,6,7,8-hexahydropteridin-6-yl]methyl}amino)phenyl]formamido}pentanedioic acid
Traditional Name(2S)-2-{[4-({[(6S)-2-amino-5-formyl-4-oxo-1,6,7,8-tetrahydropteridin-6-yl]methyl}amino)phenyl]formamido}pentanedioic acid
SMILES[H][C@@](CCC(O)=O)(NC(=O)C1=CC=C(NC[C@@]2([H])CNC3=C(N2C=O)C(O)=NC(=N)N3)C=C1)C(O)=O
InChI IdentifierInChI=1S/C20H23N7O7/c21-20-25-16-15(18(32)26-20)27(9-28)12(8-23-16)7-22-11-3-1-10(2-4-11)17(31)24-13(19(33)34)5-6-14(29)30/h1-4,9,12-13,22H,5-8H2,(H,24,31)(H,29,30)(H,33,34)(H4,21,23,25,26,32)/t12-,13-/m0/s1
InChI KeyInChIKey=VVIAGPKUTFNRDU-STQMWFEESA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as tetrahydrofolic acids. These are heterocyclic compounds based on the 5,6,7,8-tetrahydropteroic acid skeleton conjugated with at least one L-glutamic acid unit.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassPteridines and derivatives
Sub ClassPterins and derivatives
Direct ParentTetrahydrofolic acids
Alternative Parents
Substituents
  • Tetrahydrofolic acid
  • Glutamic acid or derivatives
  • N-acyl-alpha amino acid or derivatives
  • N-acyl-alpha-amino acid
  • Hippuric acid
  • Hippuric acid or derivatives
  • Alpha-amino acid or derivatives
  • Aminobenzamide
  • Aminobenzoic acid or derivatives
  • Benzamide
  • Benzoic acid or derivatives
  • Benzoyl
  • Aniline or substituted anilines
  • Phenylalkylamine
  • Aminopyrimidine
  • Secondary aliphatic/aromatic amine
  • Pyrimidone
  • Dicarboxylic acid or derivatives
  • Benzenoid
  • Pyrimidine
  • Monocyclic benzene moiety
  • Heteroaromatic compound
  • Vinylogous amide
  • Tertiary carboxylic acid amide
  • Secondary carboxylic acid amide
  • Amino acid or derivatives
  • Amino acid
  • Carboxamide group
  • Secondary amine
  • Carboxylic acid
  • Carboxylic acid derivative
  • Azacycle
  • Organooxygen compound
  • Carbonyl group
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Amine
  • Organic oxide
  • Organopnictogen compound
  • Organic oxygen compound
  • Primary amine
  • Organonitrogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginEndogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point245°C
Boiling PointNot Available
SolubilityComplete
LogP-3.2
Predicted Properties
PropertyValueSource
Water Solubility0.3 g/LALOGPS
logP-1.1ALOGPS
logP-2.7ChemAxon
logS-3.2ALOGPS
pKa (Strongest Acidic)3.47ChemAxon
pKa (Strongest Basic)2.81ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count12ChemAxon
Hydrogen Donor Count7ChemAxon
Polar Surface Area215.55 ŲChemAxon
Rotatable Bond Count9ChemAxon
Refractivity126.46 m³·mol⁻¹ChemAxon
Polarizability46.34 ųChemAxon
Number of Rings3ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0adi-0031900000-15cbae867ecd4a003ef02016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a6r-0393400000-73f11f6c59198eafb45f2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0pb9-0591000000-ea5c6303d77ffa4af0cb2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00di-0000900000-a3ae54a4d9b2cae45b722016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00bc-1243900000-4ea7b3b1902e6a1204e52016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0007-7973000000-df3edd5bd8661611dd062016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00fr-0005900000-5985bdc6c069ecc000462021-09-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-056s-1597400000-db859aadd61942f2e80b2021-09-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-05o0-0921000000-ddf359b6fc3776d454012021-09-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-004i-0000900000-56bf354a786254d088f42021-09-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0fb9-1220900000-d93259006e38248d26b42021-09-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0f6x-5920100000-575460bfef119781af802021-09-24View Spectrum
1D NMR1H NMR Spectrum (1D, 100 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR13C NMR Spectrum (1D, 100 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR1H NMR Spectrum (1D, 200 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR13C NMR Spectrum (1D, 200 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR1H NMR Spectrum (1D, 300 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR13C NMR Spectrum (1D, 300 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR1H NMR Spectrum (1D, 400 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR13C NMR Spectrum (1D, 400 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR13C NMR Spectrum (1D, 500 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR1H NMR Spectrum (1D, 600 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR13C NMR Spectrum (1D, 600 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR1H NMR Spectrum (1D, 700 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR13C NMR Spectrum (1D, 700 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR1H NMR Spectrum (1D, 800 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR13C NMR Spectrum (1D, 800 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR1H NMR Spectrum (1D, 900 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR13C NMR Spectrum (1D, 900 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR1H NMR Spectrum (1D, 1000 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR13C NMR Spectrum (1D, 1000 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
Toxicity Profile
Route of ExposureFollowing oral administration, leucovorin is rapidly absorbed. The apparent bioavailability of leucovorin was 97% for 25 mg, 75% for 50 mg, and 37% for 100 mg.
Mechanism of ToxicityAs leucovorin is a derivative of folic acid, it can be used to increase levels of folic acid under conditions favoring folic acid inhibition (following treatment of folic acid antagonists such as methotrexate). Leucovorin enhances the activity of fluorouracil by stabilizing the bond of the active metabolite (5-FdUMP) to the enzyme thymidylate synthetase.
MetabolismHepatic and intestinal mucosal, the main metabolite being the active 5-methyltetrahydrofolate. Leucovorin is readily converted to another reduced folate, 5,10-methylenetetrahydrofolate, which acts to stabilize the binding of fluorodeoxyridylic acid to thymidylate synthase and thereby enhances the inhibition of this enzyme. Half Life: 6.2 hours
Toxicity ValuesLD50: >8000 mg/kg (oral, rats).
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the treatment of osteosarcoma (after high dose methotrexate therapy). Used to diminish the toxicity and counteract the effects of impaired methotrexate elimination and of inadvertent overdosages of folic acid antagonists, and to treat megaloblastic anemias due to folic acid deficiency. Also used in combination with 5-fluorouracil to prolong survival in the palliative treatment of patients with advanced colorectal cancer. Used in cancer chemotherapy involving the drug methotrexate.
Minimum Risk LevelNot Available
Health EffectsShould not be administered intrathecally as this may produce severe adverse effects or even death when administered. [Wikipedia]. Allergic sensitization (<1%), including anaphylactoid reactions
SymptomsExcessive amounts of leucovorin may nullify the chemotherapeutic effect of folic acid antagonists.
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00650
HMDB IDHMDB02140
PubChem Compound ID54575
ChEMBL IDCHEMBL1679
ChemSpider ID49292
KEGG IDD01211
UniProt IDNot Available
OMIM ID
ChEBI ID474191
BioCyc IDNot Available
CTD IDNot Available
Stitch IDLeucovorin
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkLeucovorin
References
Synthesis Reference

James C. Wisowaty, Roy A. Swaringen, David A. Yeowell, “Synthesis of leucovorin.” U.S. Patent US4500711, issued July, 1955.

MSDSLink
General References
  1. Jardine LF, Ingram LC, Bleyer WA: Intrathecal leucovorin after intrathecal methotrexate overdose. J Pediatr Hematol Oncol. 1996 Aug;18(3):302-4. [8689347 ]
  2. Drugs.com [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Thymidylate synthase
General Function:
Thymidylate synthase activity
Specific Function:
Contributes to the de novo mitochondrial thymidylate biosynthesis pathway.
Gene Name:
TYMS
Uniprot ID:
P04818
Molecular Weight:
35715.65 Da
References
  1. Aschele C, Debernardis D, Bandelloni R, Cascinu S, Catalano V, Giordani P, Barni S, Turci D, Drudi G, Lonardi S, Gallo L, Maley F, Monfardini S: Thymidylate synthase protein expression in colorectal cancer metastases predicts for clinical outcome to leucovorin-modulated bolus or infusional 5-fluorouracil but not methotrexate-modulated bolus 5-fluorouracil. Ann Oncol. 2002 Dec;13(12):1882-92. [12453856 ]
  2. Zhu AX, Puchalski TA, Stanton VP Jr, Ryan DP, Clark JW, Nesbitt S, Charlat O, Kelly P, Kreconus E, Chabner BA, Supko JG: Dihydropyrimidine dehydrogenase and thymidylate synthase polymorphisms and their association with 5-fluorouracil/leucovorin chemotherapy in colorectal cancer. Clin Colorectal Cancer. 2004 Feb;3(4):225-34. [15025795 ]
  3. Smorenburg CH, Peters GJ, van Groeningen CJ, Noordhuis P, Smid K, van Riel AM, Dercksen W, Pinedo HM, Giaccone G: Phase II study of tailored chemotherapy for advanced colorectal cancer with either 5-fluouracil and leucovorin or oxaliplatin and irinotecan based on the expression of thymidylate synthase and dihydropyrimidine dehydrogenase. Ann Oncol. 2006 Jan;17(1):35-42. Epub 2005 Oct 26. [16251201 ]