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Showing drug card for Tobramycin (DB00684)

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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-02-19 16:03:57
Primary Accession Number DB00684
Secondary Accession Number
  • APRD00582
Name Tobramycin
Drug Type
  • Approved
  • Investigational
  • Small Molecule
Description An aminoglycoside, broad-spectrum antibiotic produced by Streptomyces tenebrarius. It is effective against gram-negative bacteria, especially the pseudomonas species. It is a 10% component of the antibiotic complex, nebramycin, produced by the same species. [PubChem]
Synonyms
  1. 3'-Deoxykanamycin B
  2. SPRC-AB01
  3. Tobramycin Sulfate
  4. tobramycin solution for inhalation
Brand Names
  1. Aktob
  2. Distobram
  3. Gernebcin
  4. NF 6
  5. Nebcin
  6. Nebramycin
  7. Nebramycin 6
  8. Nebramycin Factir 6
  9. Nebramycin Factor 6
  10. Nebramycin Vi
  11. Obracin
  12. Obramycin
  13. Sybryx
  14. Tenebrimycin
  15. Tenemycin
  16. Tobi
  17. Tobracin
  18. Tobradex
  19. Tobradistin
  20. Tobramaxin
  21. Tobramitsetin
  22. Tobramycetin
  23. Tobrasone
  24. Tobrex
Brand Mixtures Not Available
Chemical IUPAC Name 4-amino-2-[4,6-diamino-3-[3-amino-6-(aminomethyl)-5-hydroxyoxan-2-yl]oxy-2-hydroxycyclohexyl]oxy-6-(hydroxymethyl)oxane-3,5-diol
Chemical Formula C18H37N5O9
Chemical Structure Structure
CAS Registry Number 32986-56-4
InChI Identifier InChI=1/C18H37N5O9/c19-3-9-8(25)2-7(22)17(29-9)31-15-5(20)1-6(21)16(14(15)28)32-18-13(27)11(23)12(26)10(4-24)30-18/h5-18,24-28H,1-4,19-23H2/t5-,6+,7+,8-,9+,10+,11-,12+,13+,14-,15+,16-,17+,18+/m0/s1
InChI Key NLVFBUXFDBBNBW-PBSUHMDJBB
KEGG Drug D00063 Link Image
KEGG Compound C00397 Link Image
PubChem Compound 5496 Link Image
PubChem Substance 447098 Link Image
ChEBI ID 28864 Link Image
PharmGKB ID PA451704 Link Image
HET ID TOY Link Image
GenBank ID Not Available
Drug ID Number [DIN] 02241209 Link Image
RxList Link http://www.rxlist.com/cgi/generic/tobi.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Tobramycin Link Image
FDA Label
Material Safety Data Sheet (MSDS)
Synthesis Reference Y. Takagi et al., Bull. Chem. Soc. Japan 49, 3649 (1976)
Average Molecular Weight 467.5145
Monoisotopic Molecular Weight 467.2591
State Solid
Melting Point Not Available
Experimental Water Solubility 1E+003 mg/ml Source: PhysProp
Predicted Water Solubility 5.37e+01 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity -5.8 Source: PhysProp
Predicted LogP -2.97 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -0.94 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 NC[C@H]1O[C@H](O[C@@H]2[C@@H](N)C[C@@H](N)[C@H](O[C@H]3O[C@H](CO)[C@@H](O)[C@H](N)[C@H]3O)[C@H]2O)[C@H](N)C[C@@H]1O
Canonical SMILES NCC1OC(OC2C(N)CC(N)C(OC3OC(CO)C(O)C(N)C3O)C2O)C(N)CC1O
Drug Category
  • Aminoglycosides
  • Anti-Bacterial Agents
ATC Codes
AHFS Codes
  • 08:12.02
  • 52:04.04
Indication For the treatment of pseudomonas aeruginosa lung infections. Also being investigated for use in the treatment of sinus infections.
Pharmacology Tobramycin, an aminoglycoside antibiotic obtained from cultures of Streptomyces tenebrarius, is used in combination with other antibiotics to treat urinary tract infections, gynecologic infections, peritonitis, endocarditis, pneumonia, bacteremia and sepsis, respiratory infections including those associated with cystic fibrosis, osteomyelitis, and diabetic foot and other soft-tissue infections. It acts primarily by disrupting protein synthesis, leading to altered cell membrane permeability, progressive disruption of the cell envelope, and eventual cell death. Tobramycin has in vitro activity against a wide range of gram-negative organisms including Pseudomonas aeruginosa.
Mechanism of Action Tobramycin binds irreversibly to one of two aminoglycoside binding sites on the 30 S ribosomal subunit, inhibiting bacterial protein synthesis. Tobramycin may also destabilize bacterial memebrane by binding to 16 S 16 S r-RNA. An active transport mechanism for aminoglycoside uptake is necessary in the bacteria in order to attain a significant intracellular concentration of tobramycin.
Absorption The bioavailability of tobramycin may vary because of individual differences in nebulizer performance and airway pathology.
Toxicity LD50=441mg/kg (s.c. in mice)
Protein Binding Not Available
Biotransformation Not Available
Half Life The elimination half-life of tobramycin from serum is approximately 2 hours after intravenous (IV) administration.
Dosage Forms
Form Route
Liquid Intravenous
Liquid Ophthalmic
Ointment Ophthalmic
Powder, for solution Intravenous
Solution Ophthalmic
Solution Respiratory (inhalation)
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Acetazolamide Increased risk of nephrotoxicity
Amphotericin B Increased risk of nephrotoxicity
Atracurium The agent increases the effect of the muscle relaxant
Benazepril Increased risk of nephrotoxicity
Bumetanide Increased ototoxicity
Candesartan Increased risk of nephrotoxicity
Captopril 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
Cephalothin Group Increased risk of nephrotoxicity
Cephapirin Increased risk of nephrotoxicity
Cisplatin Increased risk of nephrotoxicity
Colistimethate Increased risk of nephrotoxicity
Cyclosporine Increased risk of nephrotoxicity
Didanosine Increased risk of nephrotoxicity
Doxacurium The agent increases the effect of the muscle relaxant
Enalapril Increased risk of nephrotoxicity
Ethacrynic acid Increased ototoxicity
Fosinopril Increased risk of nephrotoxicity
Furosemide Increased ototoxicity
Gallamine Triethiodide The agent increases the effect of the muscle relaxant
Heparin Increased risk of nephrotoxicity
Irbesartan Increased risk of nephrotoxicity
Lamivudine Increased risk of nephrotoxicity
Lisinopril Increased risk of nephrotoxicity
Lithium Increased risk of nephrotoxicity
Losartan Increased risk of nephrotoxicity
Metocurine The agent increases the effect of the muscle relaxant
Mivacurium The agent increases the effect of the muscle relaxant
Olmesartan Increased risk of nephrotoxicity
Pancuronium The agent increases the effect of the muscle relaxant
Perindopril Increased risk of nephrotoxicity
Phenytoin Increased risk of nephrotoxicity
Pipecuronium The agent increases the effect of the muscle relaxant
Quinapril Increased risk of nephrotoxicity
Ramipril Increased risk of nephrotoxicity
Rocuronium The agent increases the effect of the muscle relaxant
Spironolactone Increased risk of nephrotoxicity
Succinylcholine The agent increases the effect of the muscle relaxant
Sulfamethoxazole Increased risk of nephrotoxicity
Tacrolimus Increased risk of nephrotoxicity
Telmisartan Increased risk of nephrotoxicity
Thalidomide Thalidomide increases the renal toxicity of the aminoglycoside
Topiramate Increased risk of nephrotoxicity
Torasemide Increased ototoxicity
Trimethoprim Increased risk of nephrotoxicity
Tubocurarine The agent increases the effect of the muscle relaxant
Valsartan Increased risk of nephrotoxicity
Vancomycin Increased risk of nephrotoxicity
Vecuronium The agent increases the effect of the muscle relaxant
Food Interactions Not Available
Pathways Not Available
General References
  1. Drugs.com Link Image
  2. Wikipedia Link Image
  3. 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. Gill AE, Amyes SG: The contribution of a novel ribosomal S12 mutation to aminoglycoside resistance of Escherichia coli mutants. J Chemother. 2004 Aug;16(4):347-9. [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 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. 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]
  3. 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]
  4. 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.