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Identification
NameFolic Acid
Accession NumberDB00158  (NUTR00025)
Typesmall molecule
Groupsapproved, nutraceutical
Description

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. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
FolacinNot AvailableNot Available
FolateNot AvailableNot Available
PGANot AvailableNot Available
Pteroyl-L-glutamateNot AvailableNot Available
Pteroyl-L-glutamic acidNot AvailableNot Available
Pteroyl-L-monoglutamic acidNot AvailableNot Available
Pteroylglutamic acidNot AvailableNot Available
Vitamin B9Not AvailableNot Available
Vitamin BcNot AvailableNot Available
Vitamin MNot AvailableNot Available
SaltsNot Available
Brand namesNot Available
Brand mixturesNot Available
Categories
CAS number59-30-3
WeightAverage: 441.3975
Monoisotopic: 441.139681375
Chemical FormulaC19H19N7O6
InChI KeyInChIKey=OVBPIULPVIDEAO-LBPRGKRZSA-N
InChI
InChI=1S/C19H19N7O6/c20-19-25-15-14(17(30)26-19)23-11(8-22-15)7-21-10-3-1-9(2-4-10)16(29)24-12(18(31)32)5-6-13(27)28/h1-4,8,12,21H,5-7H2,(H,24,29)(H,27,28)(H,31,32)(H3,20,22,25,26,30)/t12-/m0/s1
IUPAC Name
(2S)-2-[(4-{[(2-amino-4-oxo-1,4-dihydropteridin-6-yl)methyl]amino}phenyl)formamido]pentanedioic acid
SMILES
NC1=NC(=O)C2=NC(CNC3=CC=C(C=C3)C(=O)N[C@@H](CCC(O)=O)C(O)=O)=CN=C2N1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassPteridines and Derivatives
SubclassPterins and Derivatives
Direct parentPteroic Acids and Derivatives
Alternative parentsN-acyl-alpha Amino Acids; Hippuric Acid Derivatives; Benzoyl Derivatives; Amino Fatty Acids; Pyrimidones; Dicarboxylic Acids and Derivatives; Primary Aromatic Amines; Pyrazines; Secondary Carboxylic Acid Amides; Polyols; Carboxylic Acids; Enolates; Secondary Amines; Polyamines
Substituentshippurate; n-acyl-alpha amino acid or derivative; n-acyl-alpha-amino acid; alpha-amino acid or derivative; benzamide; benzoyl; pyrimidone; pyrimidine; primary aromatic amine; dicarboxylic acid derivative; pyrazine; benzene; polyol; secondary carboxylic acid amide; carboxamide group; polyamine; secondary amine; enolate; carboxylic acid; carboxylic acid derivative; primary amine; amine; organonitrogen compound
Classification descriptionThis compound belongs to the pteroic acids and derivatives. These are compounds that are composed of a pterin with a 4-aminobenzoic acid (or derviative) at the 6 position on the pteridine ring.
Pharmacology
IndicationFor treatment of folic acid deficiency, megaloblastic anemia and in anemias of nutritional supplements, pregnancy, infancy, or childhood.
PharmacodynamicsFolic 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.
Mechanism of actionFolic acid, as it is biochemically inactive, is converted to tetrahydrofolic acid and methyltetrahydrofolate by dihydrofolate reductase. These folic acid congeners are transported across cells by receptor-mediated endocytosis where they are needed to maintain normal erythropoiesis, synthesize purine and thymidylate nucleic acids, interconvert amino acids, methylate tRNA, and generate and use formate. Using vitamin B12 as a cofactor, folic acid can normalize high homocysteine levels by remethylation of homocysteine to methionine via methionine synthetase.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingVery high to plasma protein
Metabolism

Hepatic

Route of eliminationFolic Acid is metabolized in the liver to 7, 8-dihydrofolic acid and eventually to 5,6,7,8-tetrahydrofolic acid with the aid of reduced diphosphopyridine nucleotide (DPNH) and folate reductases. A majority of the metabolic products appeared in the urine after 6 hours; excretion was generally complete within 24 hours. Folic Acid is also excreted in the milk of lactating mothers.
Half lifeNot Available
ClearanceNot Available
ToxicityIPR-MUS LD50 85 mg/kg,IVN-GPG LD50 120 mg/kg, IVN-MUS LD50 239 mg/kg, IVN-RAT LD50 500 mg/kg, IVN-RBT LD50 410 mg/kg
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Homocystinuria due to defect of N(5,10)-methylene THF deficiencyDiseaseSMP00543
Methotrexate Action PathwayDrug actionSMP00432
Folate MetabolismMetabolicSMP00053
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.7956
Blood Brain Barrier + 0.7609
Caco-2 permeable - 0.844
P-glycoprotein substrate Substrate 0.687
P-glycoprotein inhibitor I Non-inhibitor 0.9795
P-glycoprotein inhibitor II Non-inhibitor 0.9969
Renal organic cation transporter Non-inhibitor 0.876
CYP450 2C9 substrate Non-substrate 0.8276
CYP450 2D6 substrate Non-substrate 0.7947
CYP450 3A4 substrate Non-substrate 0.6212
CYP450 1A2 substrate Non-inhibitor 0.9281
CYP450 2C9 substrate Non-inhibitor 0.9071
CYP450 2D6 substrate Non-inhibitor 0.9435
CYP450 2C19 substrate Non-inhibitor 0.916
CYP450 3A4 substrate Non-inhibitor 0.9075
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.974
Ames test Non AMES toxic 0.8724
Carcinogenicity Non-carcinogens 0.9521
Biodegradation Not ready biodegradable 0.9191
Rat acute toxicity 2.4490 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9529
hERG inhibition (predictor II) Non-inhibitor 0.8444
Pharmacoeconomics
Manufacturers
  • App pharmaceuticals llc
  • Ben venue laboratories inc
  • Wyeth pharmaceuticals inc
  • Barr laboratories inc
  • Cadista pharmaceuticals inc
  • Contract pharmacal corp
  • Everylife
  • Excellium pharmaceutical inc
  • Halsey drug co inc
  • Impax laboratories inc
  • Invagen pharmaceuticals inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Lannett co inc
  • Eli lilly and co
  • Mk laboratories inc
  • Mutual pharmaceutical co inc
  • Nexgen pharma inc
  • Pharmax group inc
  • Pharmeral inc
  • Pioneer pharmaceuticals inc
  • Purepac pharmaceutical co
  • Sandoz inc
  • Tablicaps inc
  • Udl laboratories inc
  • Usl pharma inc
  • Valeant pharmaceuticals international
  • Vangard laboratories inc div midway medical co
  • Vintage pharmaceuticals llc
  • Vintage pharmaceuticals inc
  • Watson laboratories
  • Watson laboratories inc
  • West ward pharmaceutical corp
  • Whiteworth towne paulsen inc
  • Mission pharmacal co
Packagers
Dosage forms
FormRouteStrength
CapsuleOral
LiquidIntravenous
TabletOral
Prices
Unit descriptionCostUnit
Folic acid 5 mg/ml vial2.14USDml
Folic Acid 5 mg/ml2.04USDml
Folic acid powder1.68USDg
Folvite 5 mg/ml vial1.38USDml
Folic Acid 1 mg tablet0.15USDtablet
Folic acid 400 mcg tablet0.07USDtablet
Apo-Folic 5 mg Tablet0.04USDtablet
CVS Pharmacy folic acid 800 mcg tablet0.02USDtablet
Folic acid 0.4 mg tablet0.02USDtablet
Folic acid 0.8 mg tablet0.02USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point250 dec °CPhysProp
water solubility1.6 mg/L (at 25 °C)MERCK INDEX (1983)
logP-2.5Not Available
Predicted Properties
PropertyValueSource
water solubility7.61e-02 g/lALOGPS
logP-0.04ALOGPS
logP-0.68ChemAxon
logS-3.8ALOGPS
pKa (strongest acidic)3.37ChemAxon
pKa (strongest basic)2.09ChemAxon
physiological charge-2ChemAxon
hydrogen acceptor count12ChemAxon
hydrogen donor count6ChemAxon
polar surface area208.99ChemAxon
rotatable bond count9ChemAxon
refractivity111.01ChemAxon
polarizability42.06ChemAxon
number of rings3ChemAxon
bioavailability0ChemAxon
rule of fiveNoChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleYesChemAxon
Spectra
Spectra
References
Synthesis Reference

Carroll G. Temple, Jr., Robert D. Elliott, Jerry D. Rose, John A. Montgomery, “Preparation of tetrahydrofolic acid from folic acid.” U.S. Patent US4206307, issued April, 1956.

US4206307
General Reference
  1. Kamen B: Folate and antifolate pharmacology. Semin Oncol. 1997 Oct;24(5 Suppl 18):S18-30-S18-39. Pubmed
  2. Fenech M, Aitken C, Rinaldi J: Folate, vitamin B12, homocysteine status and DNA damage in young Australian adults. Carcinogenesis. 1998 Jul;19(7):1163-71. Pubmed
  3. Zittoun J: [Anemias due to disorder of folate, vitamin B12 and transcobalamin metabolism] Rev Prat. 1993 Jun 1;43(11):1358-63. Pubmed
  4. Alaimo K, McDowell MA, Briefel RR, Bischof AM, Caughman CR, Loria CM, Johnson CL: Dietary intake of vitamins, minerals, and fiber of persons ages 2 months and over in the United States: Third National Health and Nutrition Examination Survey, Phase 1, 1988-91. Adv Data. 1994 Nov 14;(258):1-28. Pubmed
  5. Raiten DJ, Fisher KD: Assessment of folate methodology used in the Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994). J Nutr. 1995 May;125(5):1371S-1398S. Pubmed
External Links
ResourceLink
KEGG DrugD00070
KEGG CompoundC00504
PubChem Compound6037
PubChem Substance46508092
ChemSpider5815
ChEBI27470
ChEMBLCHEMBL1622
Therapeutic Targets DatabaseDAP001309
PharmGKBPA449692
HETFOL
Drugs.comhttp://www.drugs.com/folic_acid.html
PDRhealthhttp://www.pdrhealth.com/drug_info/nmdrugprofiles/nutsupdrugs/fol_0110.shtml
WikipediaFolic_Acid
ATC CodesNot Available
AHFS Codes
  • 88:08.00
PDB Entries
FDA labelNot Available
MSDSshow(73.7 KB)
Interactions
Drug Interactions
Drug
AmobarbitalFolic acid decreases the effect of anticonvulsant, amobarbital.
AprobarbitalFolic acid decreases the effect of anticonvulsant, aprobarbital.
ButabarbitalFolic acid decreases the effect of anticonvulsant, butabarbital.
ButalbitalFolic acid decreases the effect of anticonvulsant, butalbital.
ButethalFolic acid decreases the effect of anticonvulsant, butethal.
Dihydroquinidine barbiturateFolic acid decreases the effect of anticonvulsant, dihydroquinidine barbiturate.
EthotoinFolic acid decreases the levels of hydantoin
FosphenytoinFolic acid decreases the levels of hydantoin
HeptabarbitalFolic acid decreases the effect of anticonvulsant, heptabarbital.
HexobarbitalFolic acid decreases the effect of anticonvulsant, hexobarbital.
MephenytoinFolic acid decreases the levels of hydantoin
MethohexitalFolic acid decreases the effect of anticonvulsant, methohexital.
MethylphenobarbitalFolic acid decreases the effect of anticonvulsant, methylphenobarbital.
PentobarbitalFolic acid decreases the effect of anticonvulsant, pentobarbital.
PhenobarbitalFolic acid decreases the effect of anticonvulsant, phenobarbital.
PhenytoinFolic acid may decrease the levels of phenytoin.
PrimidoneFolic acid decreases the effect of anticonvulsant, primidone.
Quinidine barbiturateFolic acid decreases the effect of anticonvulsant, quinidine barbiturate.
SecobarbitalFolic acid decreases the effect of anticonvulsant, secobarbital.
TalbutalFolic acid decreases the effect of anticonvulsant, talbutal.
Food InteractionsNot Available

1. Folate receptor beta

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: binder

Components

Name UniProt ID Details
Folate receptor beta P14207 Details

References:

  1. Dixit V, Van den Bossche J, Sherman DM, Thompson DH, Andres RP: Synthesis and grafting of thioctic acid-PEG-folate conjugates onto Au nanoparticles for selective targeting of folate receptor-positive tumor cells. Bioconjug Chem. 2006 May-Jun;17(3):603-9. Pubmed
  2. Wlodarczyk BJ, Cabrera RM, Hill DS, Bozinov D, Zhu H, Finnell RH: Arsenic-induced gene expression changes in the neural tube of folate transport defective mouse embryos. Neurotoxicology. 2006 Jul;27(4):547-57. Epub 2006 Apr 18. Pubmed
  3. Boyles AL, Billups AV, Deak KL, Siegel DG, Mehltretter L, Slifer SH, Bassuk AG, Kessler JA, Reed MC, Nijhout HF, George TM, Enterline DS, Gilbert JR, Speer MC: Neural tube defects and folate pathway genes: family-based association tests of gene-gene and gene-environment interactions. Environ Health Perspect. 2006 Oct;114(10):1547-52. Pubmed
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Folate receptor gamma

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: binder

Components

Name UniProt ID Details
Folate receptor gamma P41439 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Shen F, Ross JF, Wang X, Ratnam M: Identification of a novel folate receptor, a truncated receptor, and receptor type beta in hematopoietic cells: cDNA cloning, expression, immunoreactivity, and tissue specificity. Biochemistry. 1994 Feb 8;33(5):1209-15. Pubmed
  4. Shen F, Wu M, Ross JF, Miller D, Ratnam M: Folate receptor type gamma is primarily a secretory protein due to lack of an efficient signal for glycosylphosphatidylinositol modification: protein characterization and cell type specificity. Biochemistry. 1995 Apr 25;34(16):5660-5. Pubmed
  5. Prasad PD, Ramamoorthy S, Moe AJ, Smith CH, Leibach FH, Ganapathy V: Selective expression of the high-affinity isoform of the folate receptor (FR-alpha) in the human placental syncytiotrophoblast and choriocarcinoma cells. Biochim Biophys Acta. 1994 Aug 11;1223(1):71-5. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

1. Cytochrome P450 2E1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2E1 P05181 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Gamma-glutamyl hydrolase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Gamma-glutamyl hydrolase Q92820 Details

References:

  1. Schneider E, Ryan TJ: Gamma-glutamyl hydrolase and drug resistance. Clin Chim Acta. 2006 Dec;374(1-2):25-32. Epub 2006 Jun 10. Pubmed
  2. Eisele LE, Chave KJ, Lehning AC, Ryan TJ: Characterization of Human gamma-glutamyl hydrolase in solution demonstrates that the enzyme is a non-dissociating homodimer. Biochim Biophys Acta. 2006 Sep;1764(9):1479-86. Epub 2006 Jul 12. Pubmed
  3. Chen L, Eitenmiller RR: Optimization of the trienzyme extraction for the microbiological assay of folate in vegetables. J Agric Food Chem. 2007 May 16;55(10):3884-8. Epub 2007 Apr 17. Pubmed

3. Methylenetetrahydrofolate reductase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Methylenetetrahydrofolate reductase P42898 Details

References:

  1. West AA, Caudill MA: Genetic variation: impact on folate (and choline) bioefficacy. Int J Vitam Nutr Res. 2010 Oct;80(4-5):319-29. Pubmed
  2. Kim YI: Role of the MTHFR polymorphisms in cancer risk modification and treatment. Future Oncol. 2009 May;5(4):523-42. Pubmed

1. Canalicular multispecific organic anion transporter 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Canalicular multispecific organic anion transporter 2 O15438 Details

References:

  1. Zeng H, Chen ZS, Belinsky MG, Rea PA, Kruh GD: Transport of methotrexate (MTX) and folates by multidrug resistance protein (MRP) 3 and MRP1: effect of polyglutamylation on MTX transport. Cancer Res. 2001 Oct 1;61(19):7225-32. Pubmed

2. ATP-binding cassette sub-family C member 11

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
ATP-binding cassette sub-family C member 11 Q96J66 Details

References:

  1. Chen ZS, Guo Y, Belinsky MG, Kotova E, Kruh GD: Transport of bile acids, sulfated steroids, estradiol 17-beta-D-glucuronide, and leukotriene C4 by human multidrug resistance protein 8 (ABCC11). Mol Pharmacol. 2005 Feb;67(2):545-57. Epub 2004 Nov 10. Pubmed

3. Solute carrier family 22 member 6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 6 Q4U2R8 Details

References:

  1. Kuze K, Graves P, Leahy A, Wilson P, Stuhlmann H, You G: Heterologous expression and functional characterization of a mouse renal organic anion transporter in mammalian cells. J Biol Chem. 1999 Jan 15;274(3):1519-24. Pubmed
  2. Uwai Y, Okuda M, Takami K, Hashimoto Y, Inui K: Functional characterization of the rat multispecific organic anion transporter OAT1 mediating basolateral uptake of anionic drugs in the kidney. FEBS Lett. 1998 Nov 6;438(3):321-4. Pubmed

4. Multidrug resistance-associated protein 4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Multidrug resistance-associated protein 4 O15439 Details

References:

  1. Chen ZS, Lee K, Walther S, Raftogianis RB, Kuwano M, Zeng H, Kruh GD: Analysis of methotrexate and folate transport by multidrug resistance protein 4 (ABCC4): MRP4 is a component of the methotrexate efflux system. Cancer Res. 2002 Jun 1;62(11):3144-50. Pubmed
  2. Rius M, Nies AT, Hummel-Eisenbeiss J, Jedlitschky G, Keppler D: Cotransport of reduced glutathione with bile salts by MRP4 (ABCC4) localized to the basolateral hepatocyte membrane. Hepatology. 2003 Aug;38(2):374-84. Pubmed

5. ATP-binding cassette sub-family G member 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
ATP-binding cassette sub-family G member 2 Q9UNQ0 Details

References:

  1. Chen ZS, Robey RW, Belinsky MG, Shchaveleva I, Ren XQ, Sugimoto Y, Ross DD, Bates SE, Kruh GD: Transport of methotrexate, methotrexate polyglutamates, and 17beta-estradiol 17-(beta-D-glucuronide) by ABCG2: effects of acquired mutations at R482 on methotrexate transport. Cancer Res. 2003 Jul 15;63(14):4048-54. Pubmed

6. Proton-coupled folate transporter

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Proton-coupled folate transporter Q96NT5 Details

References:

  1. Nakai Y, Inoue K, Abe N, Hatakeyama M, Ohta KY, Otagiri M, Hayashi Y, Yuasa H: Functional characterization of human proton-coupled folate transporter/heme carrier protein 1 heterologously expressed in mammalian cells as a folate transporter. J Pharmacol Exp Ther. 2007 Aug;322(2):469-76. Epub 2007 May 2. Pubmed
  2. Ashokkumar B, Mohammed ZM, Vaziri ND, Said HM: Effect of folate oversupplementation on folate uptake by human intestinal and renal epithelial cells. Am J Clin Nutr. 2007 Jul;86(1):159-66. Pubmed

7. Mitochondrial folate transporter/carrier

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Mitochondrial folate transporter/carrier Q9H2D1 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

Comments
Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:08