Details of the Drug

General Information of Drug (ID: DMEMBJC)

Drug Name
Folic Acid
Synonyms
folic acid; 59-30-3; Folate; Pteroylglutamic acid; Vitamin M; Folacin; Folacid; PteGlu; Vitamin B9; Folvite; Pteroyl-L-glutamic acid; Vitamin Bc; Acifolic; Cytofol; Incafolic; Foliamin; Folsaure; Folicet; Millafol; Folipac; Folettes; Folsan; Folbal; Folsav; Vitamin Be; Pteroyl-L-monoglutamic acid; Mittafol; Folan; Facid; Pteroylmonoglutamic acid; Antianemia factor; Factor U; Folico (Italy); Folina (Italy); Foldine [France]; Pteroylmonoglutamate; Acfol (Spain); Foldine; Folcysteine; Folasic (Australia); Folcidin; Folaemin [Netherlands]; Nifolin; [3H]folic acid
Indication
Disease Entry ICD 11 Status REF
Colorectal carcinoma N.A. Approved [1]
Folate-deficiency anemia 3A02.Y Approved [2]
Infertility GB04 Approved [1]
Inflammation 1A00-CA43.1 Approved [1]
Iron-deficiency anemia 3A00 Approved [1]
Lung cancer 2C25.0 Approved [1]
Pervasive developmental disorder 6A00-6A0Z Approved [1]
Vitamin deficiency 5B55-5B71 Approved [3]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 2/3 [4]
⏷ Show the Full List of Indication(s)
Therapeutic Class
Vitamins
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 1 Molecular Weight (mw) 441.4
Logarithm of the Partition Coefficient (xlogp) -1.1
Rotatable Bond Count (rotbonds) 9
Hydrogen Bond Donor Count (hbonddonor) 6
Hydrogen Bond Acceptor Count (hbondacc) 10
ADMET Property
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [5]
Bioavailability
75% of drug becomes completely available to its intended biological destination(s) [6]
Clearance
The drug present in the plasma can be removed from the body at the rate of 52 mL/min/kg [7]
Half-life
The concentration or amount of drug in body reduced by one-half in 2.6 hours [7]
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 11.42678 micromolar/kg/day [8]
Unbound Fraction
The unbound fraction of drug in plasma is 0.5% [7]
Vd
Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 9.7 L/kg [7]
Water Solubility
The ability of drug to dissolve in water is measured as 0.0016 mg/mL [5]
Chemical Identifiers
Formula
C19H19N7O6
IUPAC Name
(2S)-2-[[4-[(2-amino-4-oxo-3H-pteridin-6-yl)methylamino]benzoyl]amino]pentanedioic acid
Canonical SMILES
C1=CC(=CC=C1C(=O)N[C@@H](CCC(=O)O)C(=O)O)NCC2=CN=C3C(=N2)C(=O)NC(=N3)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
InChIKey
OVBPIULPVIDEAO-LBPRGKRZSA-N
Cross-matching ID
PubChem CID
135398658
ChEBI ID
CHEBI:27470
CAS Number
59-30-3
DrugBank ID
DB00158
TTD ID
D0Z0DW
VARIDT ID
DR00134
INTEDE ID
DR0742
ACDINA ID
D00291
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Folate receptor (FOLR) TTQOD3G NOUNIPROTAC Binder [9]
Proton-coupled folate transporter (SLC46A1) TTY8Z2E PCFT_HUMAN Modulator [10]
Solute carrier family 19 member 1 (SLC19A1) TT09I7D S19A1_HUMAN Modulator [11]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Sodium-coupled neutral amino acid transporter 3 (SLC38A3) DTKWJH3 S38A3_HUMAN Substrate [12]
Mitochondrial folate transporter/carrier (SLC25A32) DTM8E7H MFTC_HUMAN Substrate [13]
Folate transporter 1 (SLC19A1) DTOSN46 S19A1_HUMAN Substrate [14]
Proton-coupled folate transporter (SLC46A1) DTDJEMI PCFT_HUMAN Substrate [15]
Multidrug resistance-associated protein 5 (ABCC5) DTYVM24 MRP5_HUMAN Substrate [16]
Multidrug resistance-associated protein 3 (ABCC3) DTQ3ZHF MRP3_HUMAN Substrate [17]
Multidrug resistance-associated protein 2 (ABCC2) DTFI42L MRP2_HUMAN Substrate [18]
Multidrug resistance-associated protein 4 (ABCC4) DTCSGPB MRP4_HUMAN Substrate [19]
Multidrug resistance-associated protein 1 (ABCC1) DTSYQGK MRP1_HUMAN Substrate [20]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [21]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [22]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 2E1 (CYP2E1) DEVDYN7 CP2E1_HUMAN Substrate [23]
Dihydrofolate reductase (DHFR) DE4EGMZ DYR_HUMAN Substrate [24]
Methylenetetrahydrofolate reductase (MTHFR) DEOXTPZ MTHR_HUMAN Substrate [25]
Gamma-Glu-X carboxypeptidase (GGH) DEU7MWJ GGH_HUMAN Substrate [26]
RNA cytidine acetyltransferase (hALP) DEZV4AP NAT10_HUMAN Substrate [27]
Methionine synthase reductase (MTRR) DE6NIY9 MTRR_HUMAN Substrate [28]
Vitamin B12 methionine synthase (MTR) DEWSHL5 METH_HUMAN Substrate [29]
Folylpolyglutamate synthetase (fpgS) DEW0GI5 FPGS_LACCA Substrate [30]
Dihydrofolate reductase (folA) DERGIEC DYR_ECOLI Substrate [31], [32]
Dihydrofolate reductase (folA) DEEBFXM DYR_LACCA Substrate [33]
Dihydrofolate reductase (folA) DE1GYMX Q9PJC7_CHLMU Substrate [34], [35]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 (PLCG2) OTGVC9MY PLCG2_HUMAN Gene/Protein Processing [36]
10 kDa heat shock protein, mitochondrial (HSPE1) OT7JSZLB CH10_HUMAN Gene/Protein Processing [37]
14-3-3 protein zeta/delta OT2TKG9P 1433Z_HUMAN Gene/Protein Processing [36]
3',5'-cyclic-AMP phosphodiesterase 4A (PDE4A) OTMUUZLF PDE4A_HUMAN Gene/Protein Processing [36]
3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase FUT3 (FUT3) OTXQ6P8R FUT3_HUMAN Gene/Protein Processing [36]
3-hydroxy-3-methylglutaryl-CoA lyase, cytoplasmic (HMGCLL1) OT9SQ5PU HMGC2_HUMAN Gene/Protein Processing [36]
5'-AMP-activated protein kinase subunit beta-2 (PRKAB2) OTLVN68B AAKB2_HUMAN Gene/Protein Processing [36]
72 kDa type IV collagenase (MMP2) OT5NIWA2 MMP2_HUMAN Protein Interaction/Cellular Processes [38]
A-kinase anchor protein 12 (AKAP12) OTCVRDDX AKA12_HUMAN Gene/Protein Processing [39]
Acetyl-CoA carboxylase 2 (ACACB) OT96UIP1 ACACB_HUMAN Gene/Protein Processing [36]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG
DIG Name DIG ID PubChem CID Functional Classification
Stearic acid E00079 5281 Emulsifying agent; Solubilizing agent; Viscosity-controlling agent; lubricant
Beta-D-lactose E00099 6134 Diluent; Dry powder inhaler carrier; Lyophilization aid
Lactose monohydrate E00393 104938 Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate E00208 11177 lubricant
Silicon dioxide E00670 Not Available Anticaking agent; Opacifying agent; Viscosity-controlling agent
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Folic acid 1 mg tablet 1 mg Oral Tablet Oral
Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1 Folic acid FDA Label
2 The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
3 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4563).
4 ClinicalTrials.gov (NCT04354428) Treatment for COVID-19 in High-Risk Adult Outpatients. U.S. National Institutes of Health.
5 BDDCS applied to over 900 drugs
6 Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches
7 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
8 Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
9 Gamma-glutamyl hydrolase and drug resistance. Clin Chim Acta. 2006 Dec;374(1-2):25-32.
10 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1213).
11 Increased activity of a novel low pH folate transporter associated with lipophilic antifolate resistance in chinese hamster ovary cells. J Biol Chem. 1998 Apr 3;273(14):8106-11.
12 Purification of recombinant human N-acetyltransferase type 1 (NAT1) expressed in E. coli and characterization of its potential role in folate metabolism. Biochem Pharmacol. 1995 Jun 16;49(12):1759-67.
13 Polymorphism of SLC25A32, the folate transporter gene, is associated with plasma folate levels and bone fractures in Japanese postmenopausal women. Geriatr Gerontol Int. 2014 Oct;14(4):942-6.
14 Biology of the major facilitative folate transporters SLC19A1 and SLC46A1. Curr Top Membr. 2014;73:175-204.
15 Characterization of uptake of folates by rat and human blood-brain barrier endothelial cells. Biofactors. 2010 May-Jun;36(3):201-9.
16 The human multidrug resistance protein MRP5 transports folates and can mediate cellular resistance against antifolates. Cancer Res. 2005 May 15;65(10):4425-30.
17 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.
18 Mammalian multidrug-resistance proteins (MRPs). Essays Biochem. 2011 Sep 7;50(1):179-207.
19 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.
20 Folate concentration dependent transport activity of the Multidrug Resistance Protein 1 (ABCC1). Biochem Pharmacol. 2004 Apr 15;67(8):1541-8.
21 The effect of low pH on breast cancer resistance protein (ABCG2)-mediated transport of methotrexate, 7-hydroxymethotrexate, methotrexate diglutamate, folic acid, mitoxantrone, topotecan, and resveratrol in in vitro drug transport models. Mol Pharmacol. 2007 Jan;71(1):240-9.
22 Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
23 Chronic ethanol feeding and folate deficiency activate hepatic endoplasmic reticulum stress pathway in micropigs. Am J Physiol Gastrointest Liver Physiol. 2005 Jul;289(1):G54-63.
24 The dihydrofolate reductase 19 bp polymorphism is not associated with biomarkers of folate status in healthy young adults, irrespective of folic acid intake. J Nutr. 2015 Oct;145(10):2207-11.
25 Genetic variation: impact on folate (and choline) bioefficacy. Int J Vitam Nutr Res. 2010 Oct;80(4-5):319-29.
26 Optimization of the trienzyme extraction for the microbiological assay of folate in vegetables. J Agric Food Chem. 2007 May 16;55(10):3884-8.
27 Arylamine N-acetyltransferase in human red blood cells. Biochem Pharmacol. 1992 Sep 25;44(6):1099-104.
28 Polymorphisms in genes involved in folate metabolism as maternal risk factors for Down syndrome in China. J Zhejiang Univ Sci B. 2008 Feb;9(2):93-9.
29 Metabolic derangement of methionine and folate metabolism in mice deficient in methionine synthase reductase. Mol Genet Metab. 2007 May;91(1):85-97.
30 Mutagenesis of folylpolyglutamate synthetase indicates that dihydropteroate and tetrahydrofolate bind to the same site. Biochemistry. 2008 Feb 26;47(8):2388-96.
31 Measurement of the uptake of radioactive para-aminobenzoic acid monitors folate biosynthesis in Escherichia coli K-12. Anal Biochem. 1994 Feb 1;216(2):427-30.
32 The influence of CsgD on the expression of genes of folate metabolism and hmp in Escherichia coli K-12. Arch Microbiol. 2013 Aug;195(8):559-69.
33 Molecular cloning of the gene for dihydrofolate reductase from Lactobacillus casei. Gene. 1982 Feb;17(2):229-33.
34 Biophysical principles predict fitness landscapes of drug resistance. Proc Natl Acad Sci U S A. 2016 Mar 15;113(11):E1470-8.
35 The Genital tract virulence factor pGP3 is essential for Chlamydia muridarum colonization in the gastrointestinal tract. Infect Immun. 2017 Dec 19;86(1). pii: e00429-17.
36 Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
37 Folic acid induces cell type-specific changes in the transcriptome of breast cancer cell lines: a proof-of-concept study. J Nutr Sci. 2016 Apr 26;5:e17. doi: 10.1017/jns.2016.8. eCollection 2016.
38 Possible roles for folic acid in the regulation of trophoblast invasion and placental development in normal early human pregnancy. Biol Reprod. 2011 Jun;84(6):1148-53. doi: 10.1095/biolreprod.110.088351. Epub 2011 Feb 23.
39 Impact of extracellular folate levels on global gene expression. Mol Pharmacol. 2001 Dec;60(6):1288-95. doi: 10.1124/mol.60.6.1288.