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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-06-23 18:06:49
Primary Accession Number DB00233
Secondary Accession Number
  • APRD00749
  • EXPT00693
Name Aminosalicylic Acid
Drug Type
  • Approved
  • Small Molecule
Description An antitubercular agent often administered in association with isoniazid. The sodium salt of the drug is better tolerated than the free acid. [PubChem]
Synonyms
  1. 4-ASA
  2. 4-aminosalicylic acid
  3. APAS
  4. Amino-PAS
  5. Aminosalicylate Sodium
  6. P-Aminosalicylic Acid
  7. PAS
  8. PASK
  9. Para-Amino Salicylic Acid
  10. Para-aminosalicylic acid
Brand Names
  1. Aminopar
  2. Aminox
  3. Apacil
  4. Deapasil
  5. Entepas
  6. Ferrosan
  7. Gabbropas
  8. Hellipidyl
  9. Kyselina P-Aminosalicylova
  10. Neopasalate
  11. Osacyl
  12. PAS-C
  13. Pamacyl
  14. Pamisyl
  15. Para-Pas
  16. Paramycin
  17. Parasal
  18. Parasalicil
  19. Parasalindon
  20. Pasa
  21. Pasalon
  22. Pasara
  23. Pascorbic
  24. Pasdium
  25. Pasem
  26. Paser
  27. Pasmed
  28. Pasnodia
  29. Pasolac
  30. Propasa
  31. Rezipas
  32. Sanipirol-4
  33. Sanipriol-4
Brand Mixtures Not Available
Chemical IUPAC Name 4-amino-2-hydroxybenzoic acid
Chemical Formula C7H7NO3
Chemical Structure Structure
CAS Registry Number 65-49-6
InChI Identifier InChI=1/C7H7NO3/c8-4-1-2-5(7(10)11)6(9)3-4/h1-3,9H,8H2,(H,10,11)/f/h10H
InChI Key WUBBRNOQWQTFEX-KZFATGLACO
KEGG Drug D00162 Link Image
KEGG Compound C02518 Link Image
PubChem Compound 4649 Link Image
PubChem Substance 5528 Link Image
ChEBI ID Not Available
PharmGKB ID PA448382 Link Image
HET ID BHA Link Image
GenBank ID Not Available
Drug ID Number [DIN] Not Available
RxList Link http://www.rxlist.com/cgi/generic2/paser.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Aminosalicylic_acid Link Image
FDA Label Not Available
Material Safety Data Sheet (MSDS)
Synthesis Reference Biniecki S., et al. Acta Pol Pharm. 1967;24(5):469-73
Average Molecular Weight 153.1354
Monoisotopic Molecular Weight 153.0426
State Solid
Melting Point 150.5 oC
Experimental Water Solubility 1690 mg/L Source: PhysProp
Predicted Water Solubility 1.18e+01 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 1.6 Source: PhysProp
Predicted LogP 0.62 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -1.11 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point 2.05
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID 1SXK Link Image
Experimental PDB File Show
Experimental PDB Structure
Isomeric SMILES NC1=CC(O)=C(C=C1)C(O)=O
Canonical SMILES NC1=CC(O)=C(C=C1)C(O)=O
Drug Category
  • Antitubercular Agents
  • Antituberculosis Agents
ATC Codes
AHFS Codes Not Available
Indication For the treatment of tuberculosis
Pharmacology Aminosalicylic acid is an anti-mycobacterial agent used with other anti-tuberculosis drugs (most often isoniazid) for the treatment of all forms of active tuberculosis due to susceptible strains of tubercle bacilli. The two major considerations in the clinical pharmacology of aminosalicylic acid are the prompt production of a toxic inactive metabolite under acid conditions and the short serum half life of one hour for the free drug. Aminosalicylic acid is bacteriostatic against Mycobacterium tuberculosis (prevents the multiplying of bacteria without destroying them). It also inhibits the onset of bacterial resistance to streptomycin and isoniazid.
Mechanism of Action There are two mechanisms responsible for aminosalicylic acid's bacteriostatic action against Mycobacterium tuberculosis. Firstly, aminosalicylic acid inhibits folic acid synthesis (without potentiation with antifolic compounds). The binding of para-aminobenzoic acid to pteridine synthetase acts as the first step in folic acid synthesis. Aminosalicylic acid binds pteridine synthetase with greater affinity than para-aminobenzoic acid, effectively inhibiting the synthesis of folic acid. As bacteria are unable to use external sources of folic acid, cell growth and multiplication slows. Secondly, aminosalicylic acid may inhibit the synthesis of the cell wall component, mycobactin, thus reducing iron uptake by M. tuberculosis.
Absorption Not Available
Toxicity LD50=4 gm/kg (orally in mice); LD50=3650 mg/kg (orally in rabbits)
Protein Binding 50-60%
Biotransformation Hepatic.
Half Life Not Available
Dosage Forms
Form Route
Granule Oral
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Azathioprine The 5-ASA derivative increases the toxicity of thiopurine
Mercaptopurine The 5-ASA derivative increases the toxicity of thiopurine
Thioguanine The 5-ASA derivative increases the toxicity of thiopurine
Food Interactions
  • Take without regard to meals.
Pathways Not Available
General References
  1. http://www.drugs.com/mtm/aminosalicylic-acid.html
  2. Wikipedia Link Image
  3. RxList Link Image
Organisms Affected
  • Mycobacteria
Targets
  1. 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase
  2. Phospholipase A2 VRV-PL-VIIIa
  3. P-hydroxybenzoate hydroxylase
Drug Target 1 [top]
Target 1 ID 61
Target 1 Name 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase
Target 1 Synonyms
  1. 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase
  2. 7,8-dihydro-6-hydroxymethylpterin-pyrophosphokinase
  3. EC 2.7.6.3
  4. HPPK
  5. PPPK
Target 1 Gene Name folK
Target 1 Protein Sequence >2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase 
MTRVVLSVGSNLGDRLARLRSVADGLGDALIAASPIYEADPWGGVEQGQFLNAVLIADDP
TCEPREWLRRAQEFERAAGRVRGQRWGPRNLDVDLIACYQTSATEALVEVTARENHLTLP
HPLAHLRAFVLIPWIAVDPTAQLTVAGCPRPVTRLLAELEPADRDSVRLFRPSFDLNSRH
PVSRAPES
Target 1 Number of Residues 191
Target 1 Molecular Weight 20732
Target 1 Theoretical pI 6.12
Target 1 GO Classification
Function
catalytic activity
transferase activity
transferase activity, transferring phosphorus-containing groups
kinase activity
2-amino-4-hydroxy-6-hydroxymethyldihydropteridine diphosphokinase activity
Process
physiological process
metabolism
cellular metabolism
aromatic compound metabolism
folic acid and derivative metabolism
folic acid and derivative biosynthesis
Component
Not Available
Target 1 General Function Coenzyme transport and metabolism
Target 1 Specific Function Not Available
Target 1 Pathways
Name SMPDB Link KEGG Link
Folate biosynthesis map00790 Link Image
Target 1 Reactions
  • ATP + 2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine = AMP + (2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • None
Target 1 Essentiality Essential
Target 1 GenBank ID Protein 2113971 Link Image
Target 1 UniProtKB/Swiss-Prot ID P64143 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name HPPK_MYCTU Link Image
Target 1 PDB ID Not Available
Target 1 Cellular Location Not Available
Target 1 Gene Sequence >567 bp 
TCAGCTTTCCGGTGCCCGACTGACGGGGTGTCTGCTATTCAGATCGAACGACGGCCTAAA
CAACCGCACACTGTCGCGGTCGGCGGGCTCCAGCTCGGCCAGCAGTCGCGTGACGGGCCG
CGGGCACCCGGCAACCGTCAGCTGCGCCGTTGGGTCGACGGCAATCCACGGGATCAACAC
AAAGGCCCGCAGATGCGCCAGTGGGTGCGGCAGCGTGAGGTGGTTCTCCCGCGCGGTCAC
TTCGACCAGAGCCTCGGTGGCCGAGGTCTGGTAGCAGGCGATCAGGTCGACGTCGAGATT
TCGTGGACCCCAGCGCTGGCCACGCACCCTGCCCGCAGCGCGCTCGAACTCCTGCGCCCG
CCGCAGCCACTCCCGCGGTTCGCAGGTAGGATCGTCGGCGATCAGCACCGCATTGAGGAA
CTGCCCCTGCTCCACCCCACCCCAGGGGTCGGCCTCATATATCGGGGAAGCCGCAATCAA
CGCATCGCCGAGACCGTCGGCGACCGACCGCAATCGTGCCAGGCGGTCACCCAGGTTGGA
GCCAACCGAGAGCACTACCCGCGTCAT
Target 1 GenBank Gene ID
Target 1 GeneCard ID Not Available
Target 1 GenAtlas ID Not Available
Target 1 HGNC ID Not Available
Target 1 Chromosome Location Not Available
Target 1 Locus Not Available
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Fleischmann RD, Alland D, Eisen JA, Carpenter L, White O, Peterson J, DeBoy R, Dodson R, Gwinn M, Haft D, Hickey E, Kolonay JF, Nelson WC, Umayam LA, Ermolaeva M, Salzberg SL, Delcher A, Utterback T, Weidman J, Khouri H, Gill J, Mikula A, Bishai W, Jacobs Jr WR Jr, Venter JC, Fraser CM: Whole-genome comparison of Mycobacterium tuberculosis clinical and laboratory strains. J Bacteriol. 2002 Oct;184(19):5479-90. [PubMed Link Image]
  2. Cole ST, Brosch R, Parkhill J, Garnier T, Churcher C, Harris D, Gordon SV, Eiglmeier K, Gas S, Barry CE 3rd, Tekaia F, Badcock K, Basham D, Brown D, Chillingworth T, Connor R, Davies R, Devlin K, Feltwell T, Gentles S, Hamlin N, Holroyd S, Hornsby T, Jagels K, Krogh A, McLean J, Moule S, Murphy L, Oliver K, Osborne J, Quail MA, Rajandream MA, Rogers J, Rutter S, Seeger K, Skelton J, Squares R, Squares S, Sulston JE, Taylor K, Whitehead S, Barrell BG: Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature. 1998 Jun 11;393(6685):537-44. [PubMed Link Image]
Target 1 Drug References
  1. 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 Link Image]
  2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed Link Image]
Drug Target 2 [top]
Target 2 ID 2394
Target 2 Name Phospholipase A2 VRV-PL-VIIIa
Target 2 Synonyms
  1. DPLA2
  2. EC 3.1.1.4
  3. Phosphatidylcholine 2- acylhydrolase
Target 2 Gene Name Not Available
Target 2 Protein Sequence >Phospholipase A2 VRV-PL-VIIIa 
SLLEFGKMILEETGKLAIPSYSSYGCYCGWGGKGTPKDATDRCCFVHDCCYGNLPDCNPK
SDRYKYKRVNGAIVCEKGTSCENRICECDKAAAICFRQNLNTYSKKYMLYPDFLCKGELK
C
Target 2 Number of Residues 123
Target 2 Molecular Weight 13611
Target 2 Theoretical pI 8.06
Target 2 GO Classification
Function
binding
ion binding
cation binding
calcium ion binding
catalytic activity
hydrolase activity
hydrolase activity, acting on ester bonds
carboxylic ester hydrolase activity
lipase activity
phospholipase activity
phospholipase A2 activity
Process
physiological process
metabolism
primary metabolism
lipid metabolism
lipid catabolism
Component
Not Available
Target 2 General Function Involved in phospholipase A2 activity
Target 2 Specific Function PA2 catalyzes the calcium-dependent hydrolysis of the 2- acyl groups in 3-sn-phosphoglycerides. This toxin shows neurotoxic symptoms and damages vital organs such as lung, liver and kidney. Displays edema-inducing activities when injected into the foot pads of mice and induces necrosis of muscle cells when injected into the thigh muscle
Target 2 Pathways
Name SMPDB Link KEGG Link
Glycerophospholipid metabolism map00564 Link Image
Target 2 Reactions
  • phosphatidylcholine + H2O = 1-acylglycerophosphocholine + a carboxylate
Target 2 Pfam Domain Function
Target 2 Signals
  • None
Target 2 Transmembrane Regions
  • None
Target 2 Essentiality Essential
Target 2 GenBank ID Protein Not Available
Target 2 UniProtKB/Swiss-Prot ID P59071 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name PA28_DABRP Link Image
Target 2 PDB ID 1Y38 Link Image
Target 2 PDB File Show
Target 2 3D Structure
Target 2 Cellular Location
  • Secreted protein
Target 2 Gene Sequence Not Available
Target 2 GenBank Gene ID
Target 2 GeneCard ID Not Available
Target 2 GenAtlas ID Not Available
Target 2 HGNC ID Not Available
Target 2 Chromosome Location Not Available
Target 2 Locus Not Available
Target 2 SNPs Not Available
Target 2 General References
  1. Kasturi S, Gowda TV: Purification and characterization of a major phospholipase A2 from Russell's viper (Vipera russelli) venom. Toxicon. 1989;27(2):229-37. [PubMed Link Image]
  2. Gowda VT, Schmidt J, Middlebrook JL: Primary sequence determination of the most basic myonecrotic phospholipase A2 from the venom of Vipera russelli. Toxicon. 1994 Jun;32(6):665-73. [PubMed Link Image]
Target 2 Drug References Not Available
Drug Target 3 [top]
Target 3 ID 2769
Target 3 Name P-hydroxybenzoate hydroxylase
Target 3 Synonyms
  1. 4-hydroxybenzoate 3- monooxygenase
  2. EC 1.14.13.2
Target 3 Gene Name pobA
Target 3 Protein Sequence >P-hydroxybenzoate hydroxylase 
MKTQVAIIGAGPSGLLLGQLLHKAGIDNVILERQTPDYVLGRIRAGVLEQGMVDLLREAG
VDRRMARDGLVHEGVEIAFAGQRRRIDLKRLSGGKTVTVYGQTEVTRDLMEAREACGATT
VYQAAEVRLHDLQGERPYVTFERDGERLRLDCDYIAGCDGFHGISRQSIPAERLKVFERV
YPFGWLGLLADTPPVSHELIYANHPRGFALCSQRSATRSRYYVQVPLTEKVEDWSDERFW
TELKARLPAEVAEKLVTGPSLEKSIAPLRSFVVEPMQHGRLFLAGDAAHIVPPTGAKGLN
LAASDVSTLYRLLLKAYREGRGELLERYSAICLRRIWKAERFSWWMTSVLHRFPDTDAFS
QRIQQTELEYYLGSEAGLATIAENYVGLPYEEIE
Target 3 Number of Residues 400
Target 3 Molecular Weight 44322
Target 3 Theoretical pI 6.80
Target 3 GO Classification
Function
catalytic activity
oxidoreductase activity
monooxygenase activity
Process
aromatic compound metabolism
physiological process
metabolism
cellular metabolism
generation of precursor metabolites and energy
electron transport
Component
Not Available
Target 3 General Function Coenzyme transport and metabolism
Target 3 Specific Function 4-hydroxybenzoate + NADPH + O(2) = protocatechuate + NADP(+) + H(2)O
Target 3 Pathways
Name SMPDB Link KEGG Link
Benzoate degradation via hydroxylation map00362 Link Image
Target 3 Reactions
  • 4-hydroxybenzoate + NADPH + H+ + O2 = protocatechuate + NADP+ + H2O
Target 3 Pfam Domain Function
Target 3 Signals
  • None
Target 3 Transmembrane Regions
  • None
Target 3 Essentiality Essential
Target 3 GenBank ID Protein 49145 Link Image
Target 3 UniProtKB/Swiss-Prot ID P00438 Link Image
Target 3 UniProtKB/Swiss-Prot Entry Name PHHY_PSEFL Link Image
Target 3 PDB ID 2PHH Link Image
Target 3 PDB File Show
Target 3 3D Structure
Target 3 Cellular Location Not Available
Target 3 Gene Sequence >1185 bp 
ATGAAGACTCAAGTCGCCATCATCGGCGCCGGTCCGTCCGGCCTCCTGCTCGGCCAGTTG
CTGCACAAGGCCGGCATCGACAACGTGATCCTCGAACGCCAGACCCCGGACTACGTGCTC
GGCCGCATCCGCGCCGGCGTGCTGGAACAGGGTATGGTCGACCTGCTGCGCGAGGCCGGC
GTCGACCGGCGCATGGCGCGCGACGGGCTGGTCCACGAAGGCGTGGAGATCGCCTTCGCC
GGGCAGCGCCGGCGCATCGACCTGAAGCGCCTGAGCGGCGGCAAGACGGTGACGGTCTAC
GGCCAGACCGAGGTCACCCGCGACCTCATGGAAGCCCGCGAAGCCTGCGGCGCCACTACC
GTCTACCAGGCCGCCGAGGTGCGCCTGCACGACCTGCAAGGTGAGCGCCCCTACGTGACC
TTCGAACGCGACGGCGAACGGCTACGCCTGGATTGCGACTACATCGCCGGCTGCGATGGC
TTCCACGGCATCTCGCGGCAATCGATCCCGGCGGAGCGGCTGAAGGTCTTCGAGCGGGTC
TATCCGTTCGGCTGGCTCGGCCTGCTCGCCGACACCCCGCCGGTCAGCCACGAACTGATC
TACGCCAACCATCCGCGCGGCTTCGCCCTGTGCAGCCAGCGTTCGGCGACCCGCAGCCGC
TACTACGTACAGGTGCCATTGACAGAGAAGGTCGAGGACTGGTCCGACGAGCGCTTCTGG
ACGGAACTGAAAGCGCGCCTCCCGGCCGAGGTGGCGGAGAAACTGGTGACCGGTCCTTCG
CTGGAGAAGAGCATCGCGCCGCTGCGCAGCTTCGTGGTCGAGCCGATGCAGCATGGCCGG
CTGTTCCTCGCCGGCGACGCCGCGCACATCGTGCCGCCCACCGGCGCCAAGGGACTGAAC
CTGGCGGCCAGCGACGTCAGCACGCTCTACCGGCTGCTGCTGAAGGCCTACCGCGAAGGG
CGGGGCGAACTGCTGGAACGCTACTCGGCAATCTGCCTGCGGCGGATCTGGAAGGCCGAA
CGCTTCTCCTGGTGGATGACTTCGGTGCTGCATCGCTTCCCCGACACCGACGCGTTCAGC
CAGCGCATCCAGCAGACCGAACTGGAGTACTACCTGGGCTCCGAGGCGGGCCTGGCGACC
ATCGCCGAGAACTATGTCGGCCTGCCCTACGAGGAAATCGAGTAG
Target 3 GenBank Gene ID
Target 3 GeneCard ID Not Available
Target 3 GenAtlas ID Not Available
Target 3 HGNC ID Not Available
Target 3 Chromosome Location Not Available
Target 3 Locus Not Available
Target 3 SNPs SNPJam Report Link Image
Target 3 General References
  1. Eppink MH, Bunthol C, Schreuder HA, van Berkel WJ: Phe161 and Arg166 variants of p-hydroxybenzoate hydroxylase. Implications for NADPH recognition and structural stability. FEBS Lett. 1999 Jan 29;443(3):251-5. [PubMed Link Image]
  2. Schreuder HA, van der Laan JM, Swarte MB, Kalk KH, Hol WG, Drenth J: Crystal structure of the reduced form of p-hydroxybenzoate hydroxylase refined at 2.3 A resolution. Proteins. 1992 Oct;14(2):178-90. [PubMed Link Image]
  3. van Berkel W, Westphal A, Eschrich K, Eppink M, de Kok A: Substitution of Arg214 at the substrate-binding site of p-hydroxybenzoate hydroxylase from Pseudomonas fluorescens. Eur J Biochem. 1992 Dec 1;210(2):411-9. [PubMed Link Image]
  4. Schreuder HA, van der Laan JM, Hol WG, Drenth J: Crystal structure of p-hydroxybenzoate hydroxylase complexed with its reaction product 3,4-dihydroxybenzoate. J Mol Biol. 1988 Feb 20;199(4):637-48. [PubMed Link Image]
  5. Wierenga RK, de Jong RJ, Kalk KH, Hol WG, Drenth J: Crystal structure of p-hydroxybenzoate hydroxylase. J Mol Biol. 1979 Jun 15;131(1):55-73. [PubMed Link Image]
  6. Weijer WJ, Hofsteenge J, Beintema JJ, Wierenga RK, Drenth J: p-Hydroxybenzoate hydroxylase from Pseudomonas fluorescens. 2. Fitting of the amino-acid sequence to the tertiary structure. Eur J Biochem. 1983 Jun 1;133(1):109-18. [PubMed Link Image]
  7. Hofsteenge J, Weijer WJ, Jekel PA, Beintema JJ: p-Hydroxybenzoate hydroxylase from Pseudomonas fluorescens. 1. Completion of the elucidation of the primary structure. Eur J Biochem. 1983 Jun 1;133(1):91-108. [PubMed Link Image]
  8. Hofsteenge J, Vereijken JM, Weijer WJ, Beintema JJ, Wierenga RK, Drenth J: Primary and tertiary structure studies of p-hydroxybenzoate hydroxylase from Pseudomonas fluorescens. Isolation and alignment of the CNBr peptides; interactions of the protein with flavin adenine dinucleotide. Eur J Biochem. 1980 Dec;113(1):141-50. [PubMed Link Image]
  9. Vereijken JM, Hofsteenge J, Bak HJ, Beintema JJ: The amino-acid sequence of the three smallest CNBr peptides from p-hydroxybenzoate hydroxylase from Pseudomonas fluorescens. Eur J Biochem. 1980 Dec;113(1):151-7. [PubMed Link Image]
  10. Weijer WJ, Hofsteenge J, Vereijken JM, Jekel PA, Beintema JJ: Primary structure of p-hydroxybenzoate hydroxylase from Pseudomonas fluorescens. Biochim Biophys Acta. 1982 Jun 4;704(2):385-8. [PubMed Link Image]
  11. 7628466 Eppink MH, Schreuder HA, Van Berkel WJ: Structure and function of mutant Arg44Lys of 4-hydroxybenzoate hydroxylase implications for NADPH binding. Eur J Biochem. 1995 Jul 1;231(1):157-65.
  12. 9578477 Eppink MH, Schreuder HA, van Berkel WJ: Lys42 and Ser42 variants of p-hydroxybenzoate hydroxylase from Pseudomonas fluorescens reveal that Arg42 is essential for NADPH binding. Eur J Biochem. 1998 Apr 1;253(1):194-201.
Target 3 Drug References Not Available

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