DT-Web

DB00551 - Acetohydroxamic Acid


Identification
Name Acetohydroxamic Acid
Accession Number DB00551 (APRD00774, EXPT01688)
Type 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.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 75.0666
Groups approved
Monoisotopic Weight 75.032028409
Pharmacology
Indication Used, in addition to antibiotics or medical procedures, to treat chronic urea-splitting urinary infections.
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.
Protein binding No known binding
Biotransformation 35-65% of oral dose excreted unchanged in urine (which provides the drug's therapeutic effect).
Route of elimination Not Available
Toxicity Oral, rat: LD50 = 4.8gm/kg. Symptoms of overdose include anorexia, malaise, lethargy, diminished sense of wellbeing, tremor, anxiety, nausea, and vomiting.
Affected organisms
  • Enteric bacteria and other eubacteria
Interactions
Drug Interactions Not Available
Food Interactions Not Available

Targets


Urease alpha subunit
Name Urease alpha subunit
Gene Name ureC
Pharmacological action yes
Actions inhibitor
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • 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
  • 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
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
DTHybrid score 0.8926
Macrophage metalloelastase
Name Macrophage metalloelastase
Gene Name MMP12
Pharmacological action unknown
Actions inhibitor
References
  • 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
  • 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
  • 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
  • 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
DTHybrid score 1.642

Predictions


Id Partner name Gene Name Score
4190 NADPH oxidase organizer 1 NOXO1 0.3884
1167 Interstitial collagenase MMP1 0.068
6188 Stromelysin-2 MMP10 0.0404
6195 Matrix metalloproteinase-20 MMP20 0.0402
2970 Matrix metalloproteinase-16 MMP16 0.0336
6230 A disintegrin and metalloproteinase with thrombospondin motifs 5 ADAMTS5 0.0299
1926 Stromelysin-1 MMP3 0.0291
2154 Neutrophil collagenase MMP8 0.026
6374 Disintegrin and metalloproteinase domain-containing protein 28 ADAM28 0.0253
6190 Stromelysin-3 MMP11 0.006
6189 Matrilysin MMP7 0.0057
6200 Matrix metalloproteinase-26 MMP26 0.0056
6201 Matrix metalloproteinase-27 MMP27 0.0056
6198 Matrix metalloproteinase-24 MMP24 0.0056
6199 Matrix metalloproteinase-25 MMP25 0.0056
6191 Matrix metalloproteinase-14 MMP14 0.0056
6194 Matrix metalloproteinase-19 MMP19 0.0056
6192 Matrix metalloproteinase-15 MMP15 0.0056
6197 Matrix metalloproteinase-23 MMP23A 0.0056
6196 Matrix metalloproteinase-21 MMP21 0.0056
6202 Matrix metalloproteinase-28 MMP28 0.0056
6193 Matrix metalloproteinase-17 MMP17 0.0056
1330 Collagenase 3 MMP13 0.0047
707 72 kDa type IV collagenase MMP2 0.0045
65 Matrix metalloproteinase-9 Not Available 0.0044
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