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Showing drug card for Amikacin (DB00479)

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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-02-19 16:03:56
Primary Accession Number DB00479
Secondary Accession Number
  • APRD00550
Name Amikacin
Drug Type
  • Approved
  • Investigational
  • Small Molecule
Description A broad-spectrum antibiotic derived from kanamycin. It is reno- and oto-toxic like the other aminoglycoside antibiotics. [PubChem]
Synonyms
  1. ANTIBIOTIC BB-K8
  2. Amikacin Base
  3. Amikacin Dihydrate
  4. Amikacin Sulfate
  5. Amikacina [INN-Spanish]
  6. Amikacine [INN-French]
  7. Amikacinum [INN-Latin]
  8. BB-K8
  9. amikacin
Brand Names
  1. Amicacin
  2. Amiglyde-V
  3. Amikavet
  4. Amikin
  5. Briclin
Brand Mixtures Not Available
Chemical IUPAC Name (2S)-4-amino-N-[(1R,2S,3S,4R,5S)-5-amino-2-[(2S,3R,4S,5S,6R)-4-amino-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-4-[(2R,3R,4S,5S,6R)-6-(aminomethyl)-3,4,5-trihydroxyoxan-2-yl]oxy-3-hydroxycyclohexyl]-2-hydroxybutanamide
Chemical Formula C22H43N5O13
Chemical Structure Structure
CAS Registry Number 37517-28-5
InChI Identifier InChI=1/C22H43N5O13/c23-2-1-8(29)20(36)27-7-3-6(25)18(39-22-16(34)15(33)13(31)9(4-24)37-22)17(35)19(7)40-21-14(32)11(26)12(30)10(5-28)38-21/h6-19,21-22,28-35H,1-5,23-26H2,(H,27,36)/t6-,7+,8-,9+,10+,11-,12+,13+,14+,15-,16+,17-,18+,19-,21+,22+/m0/s1/f/h27H
InChI Key LKCWBDHBTVXHDL-VLZSSAFWDT
KEGG Drug D02543 Link Image
KEGG Compound C06820 Link Image
PubChem Compound 37768 Link Image
PubChem Substance 9038 Link Image
ChEBI ID 2637 Link Image
PharmGKB ID PA448366 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 02242971 Link Image
RxList Link http://www.rxlist.com/cgi/generic3/amikacin.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Amikacin Link Image
FDA Label Not Available
Material Safety Data Sheet (MSDS)
Synthesis Reference H. Kawaguchi, T. Naito, Ger. pat. 2,234,315; H. Kawaguchi et al., U.S. pat. 3,781,268 (both 1973 to Bristol-Myers)
Average Molecular Weight 585.6025
Monoisotopic Molecular Weight 585.2857
State Solid
Melting Point 203-204 oC
Experimental Water Solubility 1.85E+005 mg/L Source: PhysProp
Predicted Water Solubility 4.97e+01 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity -7.4 Source: PhysProp
Predicted LogP -3.22 Calculated using ALOGPS
Experimental LogS -0.5 [ADME Research, USCD]
Predicted LogS -1.07 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point Not Available
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 Not Available
Isomeric SMILES NCC[C@H](O)C(=O)N[C@@H]1C[C@H](N)[C@@H](O[C@H]2O[C@H](CN)[C@@H](O)[C@H](O)[C@H]2O)[C@H](O)[C@H]1O[C@H]1O[C@H](CO)[C@@H](O)[C@H](N)[C@H]1O
Canonical SMILES NCCC(O)C(=O)NC1CC(N)C(OC2OC(CN)C(O)C(O)C2O)C(O)C1OC1OC(CO)C(O)C(N)C1O
Drug Category
  • Aminoglycosides
  • Anti-Bacterial Agents
ATC Codes
AHFS Codes
  • 08:12.02
Indication For short-term treatment of serious infections due to susceptible strains of Gram-negative bacteria, including Pseudomonas species, Escherichia coli, species of indole-positive and indole-negative Proteus, Providencia species, Klebsiella-Enterobacter-Serratia species, and Acinetobacter (Mima-Herellea) species.
Pharmacology Amikacin is an aminoglycoside antibiotic. Aminoglycosides work by binding to the bacterial 30S ribosomal subunit, causing misreading of t-RNA, leaving the bacterium unable to synthesize proteins vital to its growth. Aminoglycosides are useful primarily in infections involving aerobic, Gram-negative bacteria, such as Pseudomonas, Acinetobacter, and Enterobacter. In addition, some mycobacteria, including the bacteria that cause tuberculosis, are susceptible to aminoglycosides. Infections caused by Gram-positive bacteria can also be treated with aminoglycosides, but other types of antibiotics are more potent and less damaging to the host. In the past the aminoglycosides have been used in conjunction with penicillin-related antibiotics in streptococcal infections for their synergistic effects, particularly in endocarditis. Aminoglycosides are mostly ineffective against anaerobic bacteria, fungi and viruses.
Mechanism of Action Aminoglycosides like Amikacin "irreversibly" bind to specific 30S-subunit proteins and 16S rRNA. Amikacin inhibits protein synthesis by binding to the 30S ribosomal subunit to prevent the formation of an initiation complex with messenger RNA. Specifically Amikacin binds to four nucleotides of 16S rRNA and a single amino acid of protein S12. This interferes with decoding site in the vicinity of nucleotide 1400 in 16S rRNA of 30S subunit. This region interacts with the wobble base in the anticodon of tRNA. This leads to interference with the initiation complex, misreading of mRNA so incorrect amino acids are inserted into the polypeptide leading to nonfunctional or toxic peptides and the breakup of polysomes into nonfunctional monosomes.
Absorption Rapidly absorbed after intramuscular administration
Toxicity Not Available
Protein Binding 0-11%
Biotransformation Not Available
Half Life 2-3 hours
Dosage Forms
Form Route
Liquid Intravenous
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Atracurium The agent increases the effect of muscle relaxant
Bumetanide Increased ototoxicity
Cefalotin Increased risk of nephrotoxicity
Cefamandole Increased risk of nephrotoxicity
Cefazolin Increased risk of nephrotoxicity
Cefonicid Increased risk of nephrotoxicity
Cefoperazone Increased risk of nephrotoxicity
Ceforanide Increased risk of nephrotoxicity
Cefotaxime Increased risk of nephrotoxicity
Cefotetan Increased risk of nephrotoxicity
Cefoxitin Increased risk of nephrotoxicity
Cefradine Increased risk of nephrotoxicity
Ceftazidime Increased risk of nephrotoxicity
Ceftizoxime Increased risk of nephrotoxicity
Ceftriaxone Increased risk of nephrotoxicity
Cefuroxime Increased risk of nephrotoxicity
Cephapirin Increased risk of nephrotoxicity
Cisplatin Increased risk of nephrotoxicity
Doxacurium The agent increases the effect of muscle relaxant
Ethacrynic acid Increased ototoxicity
Furosemide Increased ototoxicity
Gallamine Triethiodide The agent increases the effect of muscle relaxant
Metocurine The agent increases the effect of muscle relaxant
Mivacurium The agent increases the effect of muscle relaxant
Pancuronium The agent increases the effect of muscle relaxant
Pipecuronium The agent increases the effect of muscle relaxant
Rocuronium The agent increases the effect of muscle relaxant
Succinylcholine The agent increases the effect of muscle relaxant
Thalidomide Thalidomide increases the renal toxicity of the aminoglycoside
Torasemide Increased ototoxicity
Tubocurarine The agent increases the effect of muscle relaxant
Vecuronium The agent increases the effect of muscle relaxant
Food Interactions Not Available
Pathways
Name SMPDB Link KEGG Link
Amikacin Pathway SMP00253 Link Image
General References
  1. Edson RS, Terrell CL: The aminoglycosides. Mayo Clin Proc. 1999 May;74(5):519-28. [PubMed Link Image]
  2. Drugs.com Link Image
  3. Wikipedia Link Image
  4. RxList Link Image
Organisms Affected
  • Enteric bacteria and other eubacteria
Targets
  1. 30S ribosomal protein S12
  2. 16S rRNA
Drug Target 1 [top]
Target 1 ID 308
Target 1 Name 30S ribosomal protein S12
Target 1 Synonyms Not Available
Target 1 Gene Name rpsL
Target 1 Protein Sequence >30S ribosomal protein S12 
ATVNQLVRKPRARKVAKSNVPALEACPQKRGVCTRVYTTTPKKPNSALRKVCRVRLTNGF
EVTSYIGGEGHNLQEHSVILIRGGRVKDLPGVRYHTVRGALDCSGVKDRKQARSKYGVKR
PKA
Target 1 Number of Residues 125
Target 1 Molecular Weight 13606
Target 1 Theoretical pI 11.49
Target 1 GO Classification
Function
structural molecule activity
structural constituent of ribosome
binding
nucleic acid binding
Process
physiological process
metabolism
macromolecule metabolism
macromolecule biosynthesis
protein biosynthesis
Component
cell
intracellular
protein complex
ribonucleoprotein complex
ribosome
small ribosomal subunit
Target 1 General Function Translation, ribosomal structure and biogenesis
Target 1 Specific Function Cryo-EM studies suggest that S12 contacts the EF-Tu bound tRNA in the A-site during codon-recognition. This contact is most likely broken as the aminoacyl-tRNA moves into the peptidyl transferase center in the 50S subunit
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • None
Target 1 Essentiality Essential
Target 1 GenBank ID Protein 43010 Link Image
Target 1 UniProtKB/Swiss-Prot ID P0A7S3 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name RS12_ECOLI Link Image
Target 1 PDB ID 1P87 Link Image
Target 1 PDB File Show
Target 1 3D Structure
Target 1 Cellular Location
  • Cytoplasmic
Target 1 Gene Sequence >375 bp 
ATGGCAACAGTTAACCAGCTGGTACGCAAACCACGTGCTCGCAAAGTTGCGAAAAGCAAC
GTGCCTGCGCTGGAAGCATGCCCGCAAAAACGTGGCGTATGTACTCGTGTATATACTACC
ACTCCTAAAAAACCGAACTCCGCGCTGCGTAAAGTATGCCGTGTTCGTCTGACTAACGGT
TTCGAAGTGACTTCCTACATCGGTGGTGAAGGTCACAACCTGCAGGAGCACTCCGTGATC
CTGATCCGTGGCGGTCGTGTTAAAGACCTCCCGGGTGTTCGTTACCACACCGTACGTGGT
GCGCTTGACTGCTCCGGCGTTAAAGACCGTAAGCAGGCTCGTTCCAAGTATGGCGTGAAG
CGTCCTAAGGCTTAA
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. Arnold RJ, Reilly JP: Observation of Escherichia coli ribosomal proteins and their posttranslational modifications by mass spectrometry. Anal Biochem. 1999 Apr 10;269(1):105-12. [PubMed Link Image]
  2. Toivonen JM, Boocock MR, Jacobs HT: Modelling in Escherichia coli of mutations in mitoribosomal protein S12: novel mutant phenotypes of rpsL. Mol Microbiol. 1999 Mar;31(6):1735-46. [PubMed Link Image]
  3. Valle M, Sengupta J, Swami NK, Grassucci RA, Burkhardt N, Nierhaus KH, Agrawal RK, Frank J: Cryo-EM reveals an active role for aminoacyl-tRNA in the accommodation process. EMBO J. 2002 Jul 1;21(13):3557-67. [PubMed Link Image]
  4. Tung CS, Joseph S, Sanbonmatsu KY: All-atom homology model of the Escherichia coli 30S ribosomal subunit. Nat Struct Biol. 2002 Oct;9(10):750-5. [PubMed Link Image]
  5. Stark H, Rodnina MV, Wieden HJ, Zemlin F, Wintermeyer W, van Heel M: Ribosome interactions of aminoacyl-tRNA and elongation factor Tu in the codon-recognition complex. Nat Struct Biol. 2002 Nov;9(11):849-54. [PubMed Link Image]
  6. Gao H, Sengupta J, Valle M, Korostelev A, Eswar N, Stagg SM, Van Roey P, Agrawal RK, Harvey SC, Sali A, Chapman MS, Frank J: Study of the structural dynamics of the E coli 70S ribosome using real-space refinement. Cell. 2003 Jun 13;113(6):789-801. [PubMed Link Image]
  7. Post LE, Arfsten AE, Reusser F, Nomura M: DNA sequences of promoter regions for the str and spc ribosomal protein operons in E. coli. Cell. 1978 Sep;15(1):215-29. [PubMed Link Image]
  8. Timms AR, Steingrimsdottir H, Lehmann AR, Bridges BA: Mutant sequences in the rpsL gene of Escherichia coli B/r: mechanistic implications for spontaneous and ultraviolet light mutagenesis. Mol Gen Genet. 1992 Mar;232(1):89-96. [PubMed Link Image]
  9. Allen PN, Noller HF: Mutations in ribosomal proteins S4 and S12 influence the higher order structure of 16 S ribosomal RNA. J Mol Biol. 1989 Aug 5;208(3):457-68. [PubMed Link Image]
  10. Funatsu G, Yaguchi M, Wittmann-Liebold B: Primary stucture of protein S12 from the small Escherichia coli ribosomal subunit. FEBS Lett. 1977 Jan 15;73(1):12-7. [PubMed Link Image]
  11. 6989816 Post LE, Nomura M: DNA sequences from the str operon of Escherichia coli. J Biol Chem. 1980 May 25;255(10):4660-6.
  12. 7556101 Urlaub H, Kruft V, Bischof O, Muller EC, Wittmann-Liebold B: Protein-rRNA binding features and their structural and functional implications in ribosomes as determined by cross-linking studies. EMBO J. 1995 Sep 15;14(18):4578-88.
  13. 8844851 Kowalak JA, Walsh KA: Beta-methylthio-aspartic acid: identification of a novel posttranslational modification in ribosomal protein S12 from Escherichia coli. Protein Sci. 1996 Aug;5(8):1625-32.
  14. 9278503 Blattner FR, Plunkett G 3rd, Bloch CA, Perna NT, Burland V, Riley M, Collado-Vides J, Glasner JD, Rode CK, Mayhew GF, Gregor J, Davis NW, Kirkpatrick HA, Goeden MA, Rose DJ, Mau B, Shao Y: The complete genome sequence of Escherichia coli K-12. Science. 1997 Sep 5;277(5331):1453-74.
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 883
Target 2 Name 16S rRNA
Target 2 Synonyms
  1. 16S ribosomal ribonucleic acid
Target 2 Gene Name Not Available
Target 2 Protein Sequence Not Available
Target 2 Number of Residues 0
Target 2 Molecular Weight Not Available
Target 2 Theoretical pI Not Available
Target 2 GO Classification
Function
transferase activity
translation
RNA binding
Process
rRNA processing
RNA processing and modification
Component
cell
Target 2 General Function Translation, ribosomal structure and biogenesis
Target 2 Specific Function In prokaryotes, the 16S rRNA is essential for recognizing the 5' end of mRNA and hence positioning it correctly on the ribosome. The 16S rRNA has a characteristic secondary structure in which half of the nucleotides are base-paired. The 16S rRNA sequence has been highly conserved and is often used for evolutionary and species comparative analysis.
Target 2 Pathways
Name SMPDB Link KEGG Link
Ribosome map03010 Link Image
Target 2 Reactions
  • rRNA + mRNA + Amino Acids = Polypeptide
Target 2 Pfam Domain Function Not Available
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 Not Available
Target 2 UniProtKB/Swiss-Prot Entry Name Not Available
Target 2 PDB ID 1EMI Link Image
Target 2 PDB File Show
Target 2 3D Structure
Target 2 Cellular Location
  • Cytoplasmic
Target 2 Gene Sequence >16S rRNA sequence 
AAATTGAAGAGTTTGATCATGGCTCAGATTGAACGCTGGCGGCAGGCCTAACACATGCAA
GTCGAACGGTAACAGGAAACAGCTTGCTGTTTCGCTGACGAGTGGCGGACGGGTGAGTAA
TGTCTGGGAAACTGCCTGATGGAGGGGGATAACTACTGGAAACGGTAGCTAATACCGCAT
AACGTCGCAAGACCAAAGAGGGGGACCCTCGGGCCTCTTGCCATCGGATGTGCCCAGATG
GGATTAGCTTGTTGGTGGGGTAACGGCTCACCAAGGCGACGATCCCTAGCTGGTCTGAGA
GGATGACCAGCCACACTGGAACTGAGACACGGTCCAGACTCCTACGGGAGGCAGCAGTGG
GGAATATTGCACAATGGGCGCAAGCCTGATGCAGCCATGCCGCGTGTATGAAGAAGGCCT
TCGGGTTGTAAAGTACTTTCAGCGGGGAGGAAGGGAGTAAAGTTAATACCTTTGCTCATT
GACGTTACCCGCAGAAGAAGCACCGGCTAACTCCGTGCCAGCAGCCGCGGTAATACGGAG
GGTGCAAGCGTTAATCGGAATTACTGGGCGTAAAGCGCACGCAGGCGGTTTGTTAAGTCA
GATGTGAAATCCCCGGGCTCAACCTGGGAACTGCATCTGATACTGGCAAGCTTGAGTCTC
GTAGAGGGGGGTAGAATTCCAGGTGTAGCGGTGAAATGCGTAGAGATCTGGAGGAATACC
GGTGGCGAAGGCGGCCCCCTGGACGAAGACTGACGCTCAGGTGCGAAAGCGTGGGGAGCA
AACAGGATTAGATACCCTGGTAGTCCACGCCGTAAACGATGTCGACTTGGAGGTTGTGCC
CTTGAGGCGTGGCTTCCGGAGCTAACGCGTTAAGTCGACCGCCTGGGGAGTACGGCCGCA
AGGTTAAAACTCAAATGAATTGACGGGGGCCCGCACAAGCGGTGGAGCATGTGGTTTAAT
TCGATGCAACGCGAAGAACCTTACCTGGTCTTGACATCCACGGAAGTTTTCAGAGATGAG
AATGTGCCTTCGGGAACCGTGAGACAGGTGCTGCATGGCTGTCGTCAGCTCGTGTTGTGA
AATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTTATCCTTTGTTGCCAGCGGTCCGGC
CGGGAACTCAAAGGAGACTGCCAGTGATAAACTGGAGGAAGGTGGGGATGACGTCAAGTC
ATCATGGCCCTTACGACCAGGGCTACACACGTGCTACAATGGCGCATACAAAGAGAAGCG
ACCTCGCGAGAGCAAGCGGACCTCATAAAGTGCGTCGTAGTCCGGATTGGAGTCTGCAAC
TCGACTCCATGAAGTCGGAATCGCTAGTAATCGTGGATCAGAATGCCACGGTGAATACGT
TCCCGGGCCTTGTACACACCGCCCGTCACACCATGGGAGTGGGTTGCAAAAGAAGTAGGT
AGCTTAACCTTCGGGAGGGCGCTTACCACTTTGTGATTCATGACTGGGGTGAAGTCGTAA
CAAGGTAACCGTAGGGGAACCTGCGGTTGGATCACCTCCTTA
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. Gu XR, Gustafsson C, Ku J, Yu M, Santi DV: Identification of the 16S rRNA m5C967 methyltransferase from Escherichia coli. Biochemistry. 1999 Mar 30;38(13):4053-7. [PubMed Link Image]
  2. Martin JF, Barreiro C, Gonzalez-Lavado E, Barriuso M: Ribosomal RNA and ribosomal proteins in corynebacteria. J Biotechnol. 2003 Sep 4;104(1-3):41-53. [PubMed Link Image]
  3. Srivastava AK, Schlessinger D: Structure and organization of ribosomal DNA. Biochimie. 1991 Jun;73(6):631-8. [PubMed Link Image]
  4. Gutell RR, Larsen N, Woese CR: Lessons from an evolving rRNA: 16S and 23S rRNA structures from a comparative perspective. Microbiol Rev. 1994 Mar;58(1):10-26. [PubMed Link Image]
Target 2 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. Possoz C, Newmark J, Sorto N, Sherratt DJ, Tolmasky ME: Sublethal concentrations of the aminoglycoside amikacin interfere with cell division without affecting chromosome dynamics. Antimicrob Agents Chemother. 2007 Jan;51(1):252-6. Epub 2006 Oct 16. [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]
  4. Doi Y, de Oliveira Garcia D, Adams J, Paterson DL: Coproduction of novel 16S rRNA methylase RmtD and metallo-beta-lactamase SPM-1 in a panresistant Pseudomonas aeruginosa isolate from Brazil. Antimicrob Agents Chemother. 2007 Mar;51(3):852-6. Epub 2006 Dec 11. [PubMed Link Image]
  5. Bogaerts P, Galimand M, Bauraing C, Deplano A, Vanhoof R, De Mendonca R, Rodriguez-Villalobos H, Struelens M, Glupczynski Y: Emergence of ArmA and RmtB aminoglycoside resistance 16S rRNA methylases in Belgium. J Antimicrob Chemother. 2007 Mar;59(3):459-64. Epub 2007 Jan 15. [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.