Drugbank Logo

Showing drug card for Acetohydroxamic Acid (DB00551)

Legend: drug field target field enzyme field

for drugs
Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-06-23 18:05:52
Primary Accession Number DB00551
Secondary Accession Number
  • APRD00774
  • EXPT01688
Name Acetohydroxamic Acid
Drug Type
  • Approved
  • Small Molecule
Description Acetohydroxamic Acid, a synthetic drug derived from hydroxylamine and ethyl acetate, is similar in structure to urea. In the urine, it acts as an antagonist of the bacterial enzyme urease. Acetohydroxamic Acid has no direct antimicrobial action and does not acidify urine directly. It is used, in addition to antibiotics or medical procedures, to treat chronic urea-splitting urinary infections.
Synonyms
  1. AHA
  2. Acethydroxamsaure
  3. Acetic acid, oxime
  4. Acetohydroxamate
  5. Acetohydroximic acid
  6. Acetyl hydroxyamino
  7. Acetylhydroxamic acid
  8. Cetohyroxamic acid
  9. Methylhydroxamic acid
  10. N-Hydroxyacetamide
Brand Names
  1. Lithostat
Brand Mixtures Not Available
Chemical IUPAC Name N-hydroxyacetamide
Chemical Formula C2H5NO2
Chemical Structure Structure
CAS Registry Number 546-88-3
InChI Identifier InChI=1/C2H5NO2/c1-2(4)3-5/h5H,1H3,(H,3,4)/f/h3H
InChI Key RRUDCFGSUDOHDG-TULZNQERCP
KEGG Drug D00220 Link Image
KEGG Compound C06808 Link Image
PubChem Compound 1990 Link Image
PubChem Substance 9027 Link Image
ChEBI ID 27777 Link Image
PharmGKB ID Not Available
HET ID HAE Link Image
GenBank ID Not Available
Drug ID Number [DIN] Not Available
RxList Link Not Available
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Acetohydroxamic_acid Link Image
FDA Label Not Available
Material Safety Data Sheet (MSDS)
Synthesis Reference Not Available
Average Molecular Weight 75.0666
Monoisotopic Molecular Weight 75.0320
State Solid
Melting Point 90.5 oC
Experimental Water Solubility 1E+006 mg/L Source: PhysProp
Predicted Water Solubility 5.09e+02 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity -0.7 Source: PhysProp
Predicted LogP -1.45 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS 0.83 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point 8.7
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 1Y93 Link Image
Experimental PDB File Show
Experimental PDB Structure
Isomeric SMILES CC(=O)NO
Canonical SMILES CC(=O)NO
Drug Category
  • Enzyme Inhibitors
ATC Codes
AHFS Codes Not Available
Indication Used, in addition to antibiotics or medical procedures, to treat chronic urea-splitting urinary infections.
Pharmacology Acetohydroxamic Acid, a synthetic drug derived from hydroxylamine and ethyl acetate, is similar in structure to urea. In the urine, it acts as an antagonist of the bacterial enzyme urease. Acetohydroxamic Acid has no direct antimicrobial action and does not acidify urine directly.
Mechanism of Action Acetohydroxamic Acid reversibly inhibits the bacterial enzyme urease. This inhibits the hydrolysis of urea and production of ammonia in urine infected with urea-splitting organisms, leading to a decrease in pH and ammonia levels. As antimicrobial agents are more effective in such conditions, the effectiveness of these agents is amplified, resulting in a higher cure rate.
Absorption Well absorbed from the GI tract following oral administration.
Toxicity Oral, rat: LD50 = 4.8gm/kg. Symptoms of overdose include anorexia, malaise, lethargy, diminished sense of wellbeing, tremor, anxiety, nausea, and vomiting.
Protein Binding No known binding
Biotransformation 35-65% of oral dose excreted unchanged in urine (which provides the drug's therapeutic effect).
Half Life 5-10 hours in patients with normal renal function
Dosage Forms
Form Route
Tablet Oral
Patient Information Not Available
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions Not Available
Food Interactions Not Available
Pathways Not Available
General References
  1. http://www.medicinenet.com/acetohydroxamic_acid-oral/article.htm
  2. Wikipedia Link Image
Organisms Affected
  • Enteric bacteria and other eubacteria
Targets
  1. Urease alpha subunit
  2. Macrophage metalloelastase
Drug Target 1 [top]
Target 1 ID 370
Target 1 Name Urease alpha subunit
Target 1 Synonyms
  1. EC 3.5.1.5
  2. Urea amidohydrolase alpha subunit
Target 1 Gene Name ureC
Target 1 Protein Sequence >Urease alpha subunit 
MSNISRQAYADMFGPTVGDKVRLADTELWIEVEDDLTTYGEEVKFGGGKVIRDGMGQGQM
LAADCVDLVLTNALIVDHWGIVKADIGVKDGRIFAIGKAGNPDIQPNVTIPIGAATEVIA
AEGKIVTAGGIDTHIHWICPQQAEEALVSGVTTMVGGGTGPAAGTHATTCTPGPWYISRM
LQAADSLPVNIGLLGKGNVSQPDALREQVAAGVIGLKIHEDWGATPAAIDCALTVADEMD
IQVALHSDTLNESGFVEDTLAAIGGRTIHTFHTEGAGGGHAPDIITACAHPNILPSSTNP
TLPYTLNTIDEHLDMLMVCHHLDPDIAEDVAFAESRIRRETIAAEDVLHDLGAFSLTSSD
SQAMGRVGEVILRTWQVAHRMKVQRGALAEETGDNDNFRVKRYIAKYTINPALTHGIAHE
VGSIEVGKLADLVVWSPAFFGVKPATVIKGGMIAIAPMGDINASIPTPQPVHYRPMFGAL
GSARHHCRLTFLSQAAAANGVAERLNLRSAIAVVKGCRTVQKADMVHNSLQPNITVDAQT
YEVRVDGELITSEPADVLPMAQRYFLF
Target 1 Number of Residues 576
Target 1 Molecular Weight 60305
Target 1 Theoretical pI 5.03
Target 1 GO Classification
Function
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides
binding
ion binding
cation binding
transition metal ion binding
nickel ion binding
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides
urease activity
catalytic activity
hydrolase activity
Process
urea metabolism
physiological process
metabolism
nitrogen compound metabolism
Component
Not Available
Target 1 General Function Amino acid transport and metabolism
Target 1 Specific Function Not Available
Target 1 Pathways
Name SMPDB Link KEGG Link
Atrazine degradation map00791 Link Image
Purine metabolism SMP00050 Link Image map00230 Link Image
Urea cycle and metabolism of amino groups map00220 Link Image
Target 1 Reactions
  • urea + H2O = CO2 + 2 NH3
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • None
Target 1 Essentiality Essential
Target 1 GenBank ID Protein 149337 Link Image
Target 1 UniProtKB/Swiss-Prot ID P18314 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name URE1_KLEAE Link Image
Target 1 PDB ID 2KAU Link Image
Target 1 PDB File Show
Target 1 3D Structure
Target 1 Cellular Location
  • Cytoplasm
Target 1 Gene Sequence >1704 bp 
ATGAGTAATATTTCACGCCAGGCCTATGCCGATATGTTCGGCCCCACCGTCGGCGACAAG
GTGCGCCTGGCAGATACCGAGCTGTGGATCGAGGTGGAGGACGATTTGACCACCTACGGG
GAAGAGGTCAAATTCGGCGGCGGCAAAGTGATCCGCGACGGCATGGGCCAGGGACAGATG
CTGGCCGCCGACTGTGTCGACCTGGTGCTCACCAACGCGTTGATCGTCGATCACTGGGGG
ATCGTTAAGGCCGATATCGGCGTGAAGGACGGCCGGATCTTCGCCATCGGCAAAGCCGGC
AACCCCGACATCCAGCCCAACGTCACCATCCCCATCGGCGCTGCGACGGAAGTGATCGCC
GCCGAAGGAAAAATTGTCACCGCCGGCGGGATCGATACCCATATTCACTGGATCTGTCCG
CAGCAGGCGGAAGAGGCGCTGGTCTCTGGCGTGACCACCATGGTCGGCGGCGGCACCGGC
CCGGCCGCGGGCACCCATGCCACCACCTGCACCCCGGGCCCGTGGTATATCTCACGCATG
CTGCAGGCGGCCGACAGCCTGCCGGTCAATATCGGCCTGCTGGGCAAGGGAAACGTTTCT
CAGCCGGATGCCCTGCGCGAGCAGGTGGCGGCAGGCGTTATTGGCCTGAAGATCCATGAG
GACTGGGGCGCCACCCCGGCGGCGATCGACTGTGCGTTAACCGTCGCCGATGAAATGGAC
ATCCAGGTCGCCCTGCACAGCGACACCCTGAATGAATCCGGTTTTGTGGAAGACACCCTC
GCCGCCATCGGCGGGCGCACCATCCACACCTTCCATACCGAAGGGGCCGGCGGCGGCCAT
GCGCCGGACATCATCACCGCCTGCGCCCACCCGAACATTTTGCCGTCGTCCACCAACCCA
ACGCTGCCCTACACCCTCAACACCATCGATGAACATCTCGATATGCTGATGGTCTGCCAC
CATCTGGACCCGGACATCGCCGAGGACGTGGCCTTTGCCGAGTCGCGCATTCGCCGGGAA
ACCATCGCTGCGGAAGACGTGCTGCACGATCTCGGCGCCTTCTCGCTCACCTCCTCCGAT
TCGCAGGCCATGGGCCGCGTCGGGGAAGTGATTCTCCGCACCTGGCAGGTGGCGCATCGC
ATGAAGGTGCAGCGCGGAGCGCTGGCGGAGGAGACCGGGGATAACGACAACTTCCGCGTG
AAGCGCTACATCGCCAAATACACCATCAACCCGGCGCTGACCCACGGCATCGCACACGAA
GTCGGATCCATTGAGGTGGGTAAGCTGGCTGACCTCGTGGTCTGGTCACCAGCCTTCTTC
GGCGTGAAACCGGCCACCGTGATCAAAGGCGGCATGATCGCCATCGCGCCGATGGGCGAT
ATCAATGCCTCTATTCCGACCCCGCAGCCGGTGCACTACCGCCCGATGTTTGGCGCGCTG
GGCAGCGCCCGCCATCACTGCCGCCTCACCTTCCTGTCGCAGGCGGCGGCAGCCAATGGC
GTTGCCGAGCGGCTGAACCTGCGCAGCGCGATCGCCGTGGTGAAAGGCTGCCGTACGGTG
CAGAAAGCCGACATGGTGCACAACAGTCTGCAGCCTAACATCACCGTCGACGCCCAGACC
TATGAGGTGCGGGTGGATGGCGAACTTATCACCAGCGAGCCGGCAGACGTTCTGCCGATG
GCGCAACGATATTTTCTGTTTTAA
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. Yamaguchi K, Cosper NJ, Stalhandske C, Scott RA, Pearson MA, Karplus PA, Hausinger RP: Characterization of metal-substituted Klebsiella aerogenes urease. J Biol Inorg Chem. 1999 Aug;4(4):468-77. [PubMed Link Image]
  2. Pearson MA, Park IS, Schaller RA, Michel LO, Karplus PA, Hausinger RP: Kinetic and structural characterization of urease active site variants. Biochemistry. 2000 Jul 25;39(29):8575-84. [PubMed Link Image]
  3. Lee MH, Mulrooney SB, Renner MJ, Markowicz Y, Hausinger RP: Klebsiella aerogenes urease gene cluster: sequence of ureD and demonstration that four accessory genes (ureD, ureE, ureF, and ureG) are involved in nickel metallocenter biosynthesis. J Bacteriol. 1992 Jul;174(13):4324-30. [PubMed Link Image]
  4. Mulrooney SB, Hausinger RP: Sequence of the Klebsiella aerogenes urease genes and evidence for accessory proteins facilitating nickel incorporation. J Bacteriol. 1990 Oct;172(10):5837-43. [PubMed Link Image]
  5. Jabri E, Carr MB, Hausinger RP, Karplus PA: The crystal structure of urease from Klebsiella aerogenes. Science. 1995 May 19;268(5213):998-1004. [PubMed Link Image]
  6. Jabri E, Karplus PA: Structures of the Klebsiella aerogenes urease apoenzyme and two active-site mutants. Biochemistry. 1996 Aug 20;35(33):10616-26. [PubMed Link Image]
  7. Pearson MA, Schaller RA, Michel LO, Karplus PA, Hausinger RP: Chemical rescue of Klebsiella aerogenes urease variants lacking the carbamylated-lysine nickel ligand. Biochemistry. 1998 Apr 28;37(17):6214-20. [PubMed Link Image]
Target 1 Drug References
  1. Palinska KA, Jahns T, Rippka R, Tandeau De Marsac N: Prochlorococcus marinus strain PCC 9511, a picoplanktonic cyanobacterium, synthesizes the smallest urease. Microbiology. 2000 Dec;146 Pt 12:3099-107. [PubMed Link Image]
  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 Link Image]
  3. 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 2203
Target 2 Name Macrophage metalloelastase
Target 2 Synonyms
  1. EC 3.4.24.65
  2. HME
  3. ME
  4. MMP-12
  5. Macrophage elastase
  6. Macrophage metalloelastase precursor
  7. Matrix metalloproteinase-12
Target 2 Gene Name MMP12
Target 2 Protein Sequence >Macrophage metalloelastase precursor 
MKFLLILLLQATASGALPLNSSTSLEKNNVLFGERYLEKFYGLEINKLPVTKMKYSGNLM
KEKIQEMQHFLGLKVTGQLDTSTLEMMHAPRCGVPDVHHFREMPGGPVWRKHYITYRINN
YTPDMNREDVDYAIRKAFQVWSNVTPLKFSKINTGMADILVVFARGAHGDFHAFDGKGGI
LAHAFGPGSGIGGDAHFDEDEFWTTHSGGTNLFLTAVHEIGHSLGLGHSSDPKAVMFPTY
KYVDINTFRLSADDIRGIQSLYGDPKENQRLPNPDNSEPALCDPNLSFDAVTTVGNKIFF
FKDRFFWLKVSERPKTSVNLISSLWPTLPSGIEAAYEIEARNQVFLFKDDKYWLISNLRP
EPNYPKSIHSFGFPNFVKKIDAAVFNPRFYRTYFFVDNQYWRYDERRQMMDPGYPKLITK
NFQGIGPKIDAVFYSKNKYYYFFQGSNQFEYDFLLQRITKTLKSNSWFGC
Target 2 Number of Residues 477
Target 2 Molecular Weight 54002
Target 2 Theoretical pI 8.98
Target 2 GO Classification
Function
binding
ion binding
cation binding
transition metal ion binding
zinc ion binding
metallopeptidase activity
catalytic activity
hydrolase activity
peptidase activity
endopeptidase activity
metalloendopeptidase activity
Process
carbohydrate metabolism
cellular carbohydrate metabolism
peptidoglycan metabolism
physiological process
metabolism
macromolecule metabolism
protein metabolism
cellular protein metabolism
proteolysis
Component
extracellular matrix
extracellular matrix (sensu Metazoa)
Target 2 General Function Involved in protease activity
Target 2 Specific Function May be involved in tissue injury and remodeling. Has significant elastolytic activity. Can accept large and small amino acids at the P1' site, but has a preference for leucine. Aromatic or hydrophobic residues are preferred at the P1 site, with small hydrophobic residues (preferably alanine) occupying P3
Target 2 Pathways Not Available
Target 2 Reactions
  • Hydrolysis of soluble and insoluble elastin [1]. Specific cleavages are also produced at -Ala14!Leu- and -Tyr16!Leu- in the B chain of insulin [2]
Target 2 Pfam Domain Function
Target 2 Signals
  • 1-16
Target 2 Transmembrane Regions
  • None
Target 2 Essentiality Non-Essential
Target 2 GenBank ID Protein 435970 Link Image
Target 2 UniProtKB/Swiss-Prot ID P39900 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name MMP12_HUMAN Link Image
Target 2 PDB ID Not Available
Target 2 Cellular Location
  • Cytoplasmic
Target 2 Gene Sequence >1413 bp 
ATGAAGTTTCTTCTAATACTGCTCCTGCAGGCCACTGCTTCTGGAGCTCTTCCCCTGAAC
AGCTCTACAAGCCTGGAAAAAAATAATGTGCTATTTGGTGAGAGATACTTAGAAAAATTT
TATGGCCTTGAGATAAACAAACTTCCAGTGACAAAAATGAAATATAGTGGAAACTTAATG
AAGGAAAAAATCCAAGAAATGCAGCACTTCTTGGGTCTGAAAGTGACCGGGCAACTGGAC
ACATCTACCCTGGAGATGATGCACGCACCTCGATGTGGAGTCCCCGATCTCCATCATTTC
AGGGAAATGCCAGGGGGGCCCGTATGGAGGAAACATTATATCACCTACAGAATCAATAAT
TACACACCTGACATGAACCGTGAGGATGTTGACTACGCAATCCGGAAAGCTTTCCAAGTA
TGGAGTAATGTTACCCCCTTGAAATTCAGCAAGATTAACACAGGCATGGCTGACATTTTG
GTGGTTTTTGCCCGTGGAGCTCATGGAGACTTCCATGCTTTTGATGGCAAAGGTGGAATC
CTAGCCCATGCTTTTGGACCTGGATCTGGCATTGGAGGGGATGCACATTTCGATGAGGAC
GAATTCTGGACTACACATTCAGGAGGCACAAACTTGTTCCTCACTGCTGTTCACGAGATT
GGCCATTCCTTAGGTCTTGGCCATTCTAGTGATCCAAAGGCTGTAATGTTCCCCACCTAC
AAATATGTCGACATCAACACATTTCGCCTCTCTGCTGATGACATACGTGGCATTCAGTCC
CTGTATGGAGACCCAAAAGAGAACCAACGCTTGCCAAATCCTGACAATTCAGAACCAGCT
CTCTGTGACCCCAATTTGAGTTTTGATGCTGTCACTACCGTGGGAAATAAGATCTTTTTC
TTCAAAGACAGGTTCTTCTGGCTGAAGGTTTCTGAGAGACCAAAGACCAGTGTTAATTTA
ATTTCTTCCTTATGGCCAACCTTGCCATCTGGCATTGAAGCTGCTTATGAAATTGAAGCC
AGAAATCAAGTTTTTCTTTTTAAAGATGACAAATACTGGTTAATTAGCAATTTAAGACCA
GAGCCAAATTATCCCAAGAGCATACATTCTTTTGGTTTTCCTAACTTTGTGAAAAAAATT
GATGCAGCTGTTTTTAACCCACGTTTTTATAGGACCTACTTCTTTGTAGATAACCAGTAT
TGGAGGTATGATGAAAGGAGACAGATGATGGACCCTGGTTATCCCAAACTGATTACCAAG
AACTTCCAAGGAATCGGGCCTAAAATTGATGCAGTCTTCTATTCTAAAAACAAATACTAC
TATTTCTTCCAAGGATCTAACCAATTTGAATATGACTTCCTACTCCAACGTATCACCAAA
ACACTGAAAAGCAATAGCTGGTTTGGTTGTTAG
Target 2 GenBank Gene ID
Target 2 GeneCard ID MMP12 Link Image
Target 2 GenAtlas ID MMP12 Link Image
Target 2 HGNC ID HGNC:7158 Link Image
Target 2 Chromosome Location 11
Target 2 Locus 11q22.3
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. Lang R, Kocourek A, Braun M, Tschesche H, Huber R, Bode W, Maskos K: Substrate specificity determinants of human macrophage elastase (MMP-12) based on the 1.1 A crystal structure. J Mol Biol. 2001 Sep 28;312(4):731-42. [PubMed Link Image]
  2. Nar H, Werle K, Bauer MM, Dollinger H, Jung B: Crystal structure of human macrophage elastase (MMP-12) in complex with a hydroxamic acid inhibitor. J Mol Biol. 2001 Sep 28;312(4):743-51. [PubMed Link Image]
  3. Shapiro SD, Kobayashi DK, Ley TJ: Cloning and characterization of a unique elastolytic metalloproteinase produced by human alveolar macrophages. J Biol Chem. 1993 Nov 15;268(32):23824-9. [PubMed Link Image]
  4. Gronski TJ Jr, Martin RL, Kobayashi DK, Walsh BC, Holman MC, Huber M, Van Wart HE, Shapiro SD: Hydrolysis of a broad spectrum of extracellular matrix proteins by human macrophage elastase. J Biol Chem. 1997 May 2;272(18):12189-94. [PubMed Link Image]
Target 2 Drug References
  1. Bertini I, Calderone V, Cosenza M, Fragai M, Lee YM, Luchinat C, Mangani S, Terni B, Turano P: Conformational variability of matrix metalloproteinases: beyond a single 3D structure. Proc Natl Acad Sci U S A. 2005 Apr 12;102(15):5334-9. Epub 2005 Apr 4. [PubMed Link Image]
  2. Mannino C, Nievo M, Machetti F, Papakyriakou A, Calderone V, Fragai M, Guarna A: Synthesis of bicyclic molecular scaffolds (BTAa): an investigation towards new selective MMP-12 inhibitors. Bioorg Med Chem. 2006 Nov 15;14(22):7392-403. Epub 2006 Aug 8. [PubMed Link Image]
  3. Fukuda M, Peppas NA, McGinity JW: Floating hot-melt extruded tablets for gastroretentive controlled drug release system. J Control Release. 2006 Oct 10;115(2):121-9. Epub 2006 Jul 21. [PubMed Link Image]
  4. Bertini I, Calderone V, Fragai M, Giachetti A, Loconte M, Luchinat C, Maletta M, Nativi C, Yeo KJ: Exploring the subtleties of drug-receptor interactions: the case of matrix metalloproteinases. J Am Chem Soc. 2007 Mar 7;129(9):2466-75. Epub 2007 Feb 2. [PubMed Link Image]

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.