Identification

Name
Aminosalicylic Acid
Accession Number
DB00233  (APRD00749, EXPT00693, DB09367)
Type
Small Molecule
Groups
Approved
Description

An antitubercular agent often administered in association with isoniazid. The sodium salt of the drug is better tolerated than the free acid.

Structure
Thumb
Synonyms
  • 4-amino-2-hydroxybenzoic acid
  • 4-aminosalicylate
  • 4-aminosalicylic acid
  • p-aminosalicylic acid
  • para-amino salicylic acid
  • para-aminosalicylic acid
  • PAS
Product Ingredients
IngredientUNIICASInChI Key
Aminosalicylate calcium73I4QDW01W133-15-3XDWVNCOPMIEDJK-UHFFFAOYSA-L
Aminosalicylate sodiumT9ZKL3TNQF133-10-8FVVDKUPCWXUVNP-UHFFFAOYSA-M
Calcium aminosalicylate trihydrate9VF16M7FWU6059-16-1IPLQYSPEGHNJCQ-UHFFFAOYSA-L
Potassium aminosalicylate7N21461LKD133-09-5PRZJIMSXCLZGLT-UHFFFAOYSA-M
Sodium aminosalicylate dihydrateS38B9W6AXW6018-19-5GMUQJDAYXZXBOT-UHFFFAOYSA-M
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
GranupasGranule, delayed release4 gOralEurocept International B. V.2014-04-07Not applicableEu
Nemasol Sodium Tab 500mgTablet500 mgOralIcn Pharmaceuticals1966-12-312005-04-26Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
PaserGranule, delayed release4 g/1OralJacobus Pharmaceutical1995-02-15Not applicableUs
International/Other Brands
Pamisyl (Parke-Davis) / Rexipas (Bristol-Myers Squibb) / Rezipas (Bristol-Myers Squibb)
Categories
UNII
5B2658E0N2
CAS number
65-49-6
Weight
Average: 153.1354
Monoisotopic: 153.042593095
Chemical Formula
C7H7NO3
InChI Key
WUBBRNOQWQTFEX-UHFFFAOYSA-N
InChI
InChI=1S/C7H7NO3/c8-4-1-2-5(7(10)11)6(9)3-4/h1-3,9H,8H2,(H,10,11)
IUPAC Name
4-amino-2-hydroxybenzoic acid
SMILES
NC1=CC(O)=C(C=C1)C(O)=O

Pharmacology

Indication

For the treatment of tuberculosis

Associated Conditions
Pharmacodynamics

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.

TargetActionsOrganism
UProstaglandin G/H synthase 2
inhibitor
Human
UInhibitor of nuclear factor kappa-B kinase subunit alpha
inhibitor
Human
UArachidonate 5-lipoxygenase
inhibitor
Human
UGroup IIE secretory phospholipase A2
unknown
Human
U2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase
unknown
Mycobacterium tuberculosis
Absorption
Not Available
Volume of distribution
Not Available
Protein binding

50-60%

Metabolism

Hepatic.

Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

LD50=4 gm/kg (orally in mice); LD50=3650 mg/kg (orally in rabbits)

Affected organisms
  • Mycobacteria
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinAminosalicylic Acid may increase the anticoagulant activities of (R)-warfarin.
(S)-WarfarinAminosalicylic Acid may increase the anticoagulant activities of (S)-Warfarin.
2,4-thiazolidinedioneAminosalicylic Acid may increase the hypoglycemic activities of 2,4-thiazolidinedione.
4-hydroxycoumarinAminosalicylic Acid may increase the anticoagulant activities of 4-hydroxycoumarin.
AbciximabThe risk or severity of bleeding can be increased when Aminosalicylic Acid is combined with Abciximab.
AcarboseAminosalicylic Acid may increase the hypoglycemic activities of Acarbose.
AceclofenacThe therapeutic efficacy of Aminosalicylic Acid can be decreased when used in combination with Aceclofenac.
AcenocoumarolAminosalicylic Acid may increase the anticoagulant activities of Acenocoumarol.
AcetazolamideThe risk or severity of adverse effects can be increased when Aminosalicylic Acid is combined with Acetazolamide.
AcetohexamideAminosalicylic Acid may increase the hypoglycemic activities of Acetohexamide.
Food Interactions
  • Take without regard to meals.

References

Synthesis Reference

Thomas M. Parkinson, Joseph P. Brown, Robert E. Wingard, Jr., "Pharmaceutical preparations containing a polymeric agent for releasing 5-aminosalicylic acid or its salts into the gastrointestinal tract." U.S. Patent US4298595, issued January, 1975.

US4298595
General References
Not Available
External Links
Human Metabolome Database
HMDB0014378
KEGG Drug
D00162
KEGG Compound
C02518
PubChem Compound
4649
PubChem Substance
46505572
ChemSpider
4488
BindingDB
48319
ChEBI
27565
ChEMBL
CHEMBL1169
PharmGKB
PA448382
HET
BHA
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
4-Aminosalicylic_acid
ATC Codes
J04AA01 — 4-aminosalicylic acidJ04AA02 — Sodium aminosalicylateJ04AA03 — Calcium aminosalicylate
PDB Entries
1pbc / 1pbf / 1sxk / 5x7z
MSDS
Download (73.6 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentHealthy Volunteers1
2CompletedTreatmentColorectal Cancers1
2CompletedTreatmentJaundice / Malignant Neoplasm of Pancreas1
2CompletedTreatmentMalignant Neoplasm of Stomach3
2TerminatedTreatmentCrohn's Disease (CD)2
4RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Tuberculosis1
Not AvailableRecruitingNot AvailableTuberculosis1

Pharmacoeconomics

Manufacturers
  • Century pharmaceuticals inc
  • Hexcel chemical products
  • Panray corp sub ormont drug and chemical co inc
  • Lannett co inc
  • Consolidated midland corp
  • Jacobus pharmaceutical co
  • Bristol myers squibb co
Packagers
  • Jacobus Pharmaceutical Co.
  • Medisca Inc.
  • Professional Co.
  • Spectrum Pharmaceuticals
Dosage forms
FormRouteStrength
Granule, delayed releaseOral4 g
TabletOral500 mg
Granule, delayed releaseOral4 g/1
Prices
Unit descriptionCostUnit
Paser granules 4 gm packet3.59USD packet
Aminosalicylic acid powder2.4USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)150.5 dec °CPhysProp
water solubility1690 mg/L (at 23 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP0.89SANGSTER (1994)
pKa2.05 (at 25 °C)KORTUM,G ET AL (1961)
Predicted Properties
PropertyValueSource
Water Solubility11.8 mg/mLALOGPS
logP0.62ALOGPS
logP0.83ChemAxon
logS-1.1ALOGPS
pKa (Strongest Acidic)3.68ChemAxon
pKa (Strongest Basic)2.19ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area83.55 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity40 m3·mol-1ChemAxon
Polarizability14.29 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9356
Blood Brain Barrier-0.7101
Caco-2 permeable-0.852
P-glycoprotein substrateNon-substrate0.8405
P-glycoprotein inhibitor INon-inhibitor0.9777
P-glycoprotein inhibitor IINon-inhibitor0.9905
Renal organic cation transporterNon-inhibitor0.9337
CYP450 2C9 substrateNon-substrate0.8174
CYP450 2D6 substrateNon-substrate0.8358
CYP450 3A4 substrateNon-substrate0.7782
CYP450 1A2 substrateNon-inhibitor0.8645
CYP450 2C9 inhibitorNon-inhibitor0.8281
CYP450 2D6 inhibitorNon-inhibitor0.9627
CYP450 2C19 inhibitorInhibitor0.5778
CYP450 3A4 inhibitorNon-inhibitor0.7324
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9157
Ames testNon AMES toxic0.9388
CarcinogenicityNon-carcinogens0.8045
BiodegradationReady biodegradable0.6246
Rat acute toxicity1.5761 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9689
hERG inhibition (predictor II)Non-inhibitor0.9676
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (9.18 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-0udi-0900000000-9edb9b6028f854f76708
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-0a4i-1900000000-e893f1439cefbeef271a
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-0a4i-5900000000-09273d1390d26a8def2d
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-066r-9200000000-e029b385a8c32e95b6b7
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-00ku-9000000000-58cccd83d40f8fade4dc
MS/MS Spectrum - , positiveLC-MS/MSsplash10-06dr-2900200000-832b5b02326d8b11bac4

Taxonomy

Description
This compound belongs to the class of organic compounds known as aminosalicylic acids. These are salicylic acids carrying an amino group on the benzene ring.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Benzoic acids and derivatives
Direct Parent
Aminosalicylic acids
Alternative Parents
4-aminosalicylic acids / Salicylic acids / Aminobenzoic acids / Benzoic acids / m-Aminophenols / Benzoyl derivatives / Aniline and substituted anilines / 1-hydroxy-2-unsubstituted benzenoids / 1-hydroxy-4-unsubstituted benzenoids / Vinylogous acids
show 8 more
Substituents
4-aminosalicylic acid / Aminosalicylic acid / Salicylic acid / Aminobenzoic acid or derivatives / Aminobenzoic acid / Benzoic acid / Aniline or substituted anilines / M-aminophenol / Aminophenol / Benzoyl
show 19 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
phenols, aminobenzoic acid (CHEBI:27565)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and...
Gene Name
PTGS2
Uniprot ID
P35354
Uniprot Name
Prostaglandin G/H synthase 2
Molecular Weight
68995.625 Da
References
  1. Mifflin RC, Saada JI, Di Mari JF, Valentich JD, Adegboyega PA, Powell DW: Aspirin-mediated COX-2 transcript stabilization via sustained p38 activation in human intestinal myofibroblasts. Mol Pharmacol. 2004 Feb;65(2):470-8. [PubMed:14742690]
  2. Generini S, Fiori G, Matucci Cerinic M: Therapy of spondylarthropathy in inflammatory bowel disease. Clin Exp Rheumatol. 2002 Nov-Dec;20(6 Suppl 28):S88-94. [PubMed:12463455]
  3. Distrutti E, Sediari L, Mencarelli A, Renga B, Orlandi S, Russo G, Caliendo G, Santagada V, Cirino G, Wallace JL, Fiorucci S: 5-Amino-2-hydroxybenzoic acid 4-(5-thioxo-5H-[1,2]dithiol-3yl)-phenyl ester (ATB-429), a hydrogen sulfide-releasing derivative of mesalamine, exerts antinociceptive effects in a model of postinflammatory hypersensitivity. J Pharmacol Exp Ther. 2006 Oct;319(1):447-58. Epub 2006 Jul 19. [PubMed:16855178]
  4. Cipolla G, Crema F, Sacco S, Moro E, de Ponti F, Frigo G: Nonsteroidal anti-inflammatory drugs and inflammatory bowel disease: current perspectives. Pharmacol Res. 2002 Jul;46(1):1-6. [PubMed:12208114]
  5. Pruzanski W, Stefanski E, Vadas P, Ramamurthy NS: Inhibition of extracellular release of proinflammatory secretory phospholipase A2 (sPLA2) by sulfasalazine: a novel mechanism of anti-inflammatory activity. Biochem Pharmacol. 1997 Jun 15;53(12):1901-7. [PubMed:9256165]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Scaffold protein binding
Specific Function
Serine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or oth...
Gene Name
CHUK
Uniprot ID
O15111
Uniprot Name
Inhibitor of nuclear factor kappa-B kinase subunit alpha
Molecular Weight
84638.88 Da
References
  1. Bantel H, Berg C, Vieth M, Stolte M, Kruis W, Schulze-Osthoff K: Mesalazine inhibits activation of transcription factor NF-kappaB in inflamed mucosa of patients with ulcerative colitis. Am J Gastroenterol. 2000 Dec;95(12):3452-7. [PubMed:11151876]
  2. Allgayer H: Review article: mechanisms of action of mesalazine in preventing colorectal carcinoma in inflammatory bowel disease. Aliment Pharmacol Ther. 2003 Sep;18 Suppl 2:10-4. [PubMed:12950415]
  3. Weber CK, Liptay S, Wirth T, Adler G, Schmid RM: Suppression of NF-kappaB activity by sulfasalazine is mediated by direct inhibition of IkappaB kinases alpha and beta. Gastroenterology. 2000 Nov;119(5):1209-18. [PubMed:11054378]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Iron ion binding
Specific Function
Catalyzes the first step in leukotriene biosynthesis, and thereby plays a role in inflammatory processes.
Gene Name
ALOX5
Uniprot ID
P09917
Uniprot Name
Arachidonate 5-lipoxygenase
Molecular Weight
77982.595 Da
References
  1. Nielsen OH, Bukhave K, Elmgreen J, Ahnfelt-Ronne I: Inhibition of 5-lipoxygenase pathway of arachidonic acid metabolism in human neutrophils by sulfasalazine and 5-aminosalicylic acid. Dig Dis Sci. 1987 Jun;32(6):577-82. [PubMed:2882965]
  2. Allgayer H, Eisenburg J, Paumgartner G: Soybean lipoxygenase inhibition: studies with the sulphasalazine metabolites N-acetylaminosalicylic acid, 5-aminosalicylic acid and sulphapyridine. Eur J Clin Pharmacol. 1984;26(4):449-51. [PubMed:6428914]
  3. Sircar JC, Schwender CF, Carethers ME: Inhibition of soybean lipoxygenase by sulfasalazine and 5-aminosalicylic acid: a possible mode of action in ulcerative colitis. Biochem Pharmacol. 1983 Jan 1;32(1):170-2. [PubMed:6131674]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Unknown
General Function
Phospholipase a2 activity
Specific Function
PA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides. Has a preference for arachidonic-containing phospholipids.
Gene Name
PLA2G2E
Uniprot ID
Q9NZK7
Uniprot Name
Group IIE secretory phospholipase A2
Molecular Weight
15988.525 Da
References
  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]
Kind
Protein
Organism
Mycobacterium tuberculosis
Pharmacological action
Unknown
Actions
Unknown
General Function
Not Available
Specific Function
2-amino-4-hydroxy-6-hydroxymethyldihydropteridine diphosphokinase activity
Gene Name
folK
Uniprot ID
P9WNC7
Uniprot Name
2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase
Molecular Weight
20731.305 Da
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:17139284]
  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:17016423]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Peroxidase activity
Specific Function
Part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In the stimulated PMN, MPO catalyzes the production o...
Gene Name
MPO
Uniprot ID
P05164
Uniprot Name
Myeloperoxidase
Molecular Weight
83867.71 Da
References
  1. von Ritter C, Grisham MB, Granger DN: Sulfasalazine metabolites and dapsone attenuate formyl-methionyl-leucyl-phenylalanine-induced mucosal injury in rat ileum. Gastroenterology. 1989 Mar;96(3):811-6. [PubMed:2563347]
  2. Gorgulu S, Yagci G, Kaymakcioglu N, Ozkara M, Kurt B, Ozcan A, Kaya O, Sadir S, Tufan T: Hyperbaric oxygen enhances the efficiency of 5-aminosalicylic acid in acetic acid-induced colitis in rats. Dig Dis Sci. 2006 Mar;51(3):480-7. [PubMed:16614956]

Drug created on June 13, 2005 07:24 / Updated on August 02, 2018 07:40