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Identification
Name Tobramycin
Accession Number DB00684 (APRD00582)
Type small molecule
Groups approved
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]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • 3'-Deoxykanamycin B
  • SPRC-AB01
  • tobramycin solution for inhalation
  • Tobramycin Sulfate
Brand names
  • Aktob
  • Distobram
  • Gernebcin
  • Nebcin
  • Nebramycin
  • Nebramycin 6
  • Nebramycin Factir 6
  • Nebramycin Factor 6
  • Nebramycin Vi
  • NF 6
  • Obracin
  • Obramycin
  • Sybryx
  • Tenebrimycin
  • Tenemycin
  • Tobi
  • Tobracin
  • Tobradex
  • Tobradistin
  • Tobramaxin
  • Tobramitsetin
  • Tobramycetin
  • Tobrasone
  • Tobrex
Brand name mixtures Not Available
Categories
  • Anti-Bacterial Agents
  • Aminoglycosides
CAS number 32986-56-4
Weight Average: 467.5145
Monoisotopic: 467.259127807
Chemical Formula C18H37N5O9
InChI Key InChIKey=NLVFBUXFDBBNBW-PBSUHMDJSA-N
InChI
InChI=1S/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
Plain Text
IUPAC Name
(2S,3R,4S,5S,6R)-4-amino-2-{[(1S,2S,3R,4S,6R)-4,6-diamino-3-{[(2R,3R,5S,6R)-3-amino-6-(aminomethyl)-5-hydroxyoxan-2-yl]oxy}-2-hydroxycyclohexyl]oxy}-6-(hydroxymethyl)oxane-3,5-diol
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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Aminoglycosides
Substructures
  • Aminoglycosides
  • Glycerol and Derivatives
  • Hydroxy Compounds
  • Pyrans
  • Acetals and Derivatives
  • Aliphatic and Aryl Amines
  • Ethers
  • Alcohols and Polyols
  • Amino Alcohols
  • Heterocyclic compounds
Pharmacology
Indication For the treatment of pseudomonas aeruginosa lung infections. Also being investigated for use in the treatment of sinus infections.
Pharmacodynamics 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.
Volume of distribution Not Available
Protein binding Not Available
Metabolism
Route of elimination Not Available
Half life The elimination half-life of tobramycin from serum is approximately 2 hours after intravenous (IV) administration.
Clearance Not Available
Toxicity LD50=441mg/kg (s.c. in mice)
Affected organisms
  • Enteric bacteria and other eubacteria
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Alcon laboratories inc
  • Akorn inc
  • Alcon universal ltd
  • Altana inc
  • Bausch and lomb pharmaceuticals inc
  • Novex pharma
  • Falcon pharmaceuticals ltd
  • Novartis pharmaceuticals corp
  • Eli lilly and co
  • Akorn strides llc
  • Apothecon inc div bristol myers squibb
  • App pharmaceuticals llc
  • Astrazeneca lp
  • Baxter healthcare corp anesthesia and critical care
  • Hospira inc
  • Marsam pharmaceuticals llc
  • Teva parenteral medicines inc
  • X gen pharmaceuticals inc
Packagers
Dosage forms
Form Route Strength
Liquid Intravenous
Liquid Ophthalmic
Ointment Ophthalmic
Powder, for solution Intravenous
Solution Ophthalmic
Solution Respiratory (inhalation)
Prices
Unit description Cost Unit
Tobi (1 Box = 56, 5ml Ampules = 280ml Total) 280ml Plastic Container 4461.42 USD plastic
Tobramycin 1.2 gm vial 338.25 USD vial
TobraDex 0.3-0.1% Suspension 10ml Bottle 200.43 USD bottle
TobraDex 0.3-0.1% Ointment 3.5 gm Tube 126.67 USD tube
TobraDex 0.3-0.1% Suspension 5ml Bottle 98.11 USD bottle
Tobrex 0.3% Ointment 3.5 gm Tube 80.02 USD tube
Tobrex 0.3% Solution 5ml Bottle 67.58 USD bottle
TobraDex 0.3-0.1% Suspension 2.5ml Bottle 54.99 USD bottle
Tobramycin sulfate powder 53.55 USD g
Tobradex eye drops 19.27 USD ml
Tobi 300 mg/5 ml solution 17.58 USD ml
Tobramycin Sulfate 0.3% Solution 5ml Bottle 15.99 USD bottle
Tobrex 0.3% eye drops 13.0 USD ml
Tobi 60 mg/ml Solution 11.4 USD ml
Tobramycin Sulfate 40 mg/ml Solution 3.6 USD ml
Tobramycin 40 mg/ml 3.14 USD ml
Tobramycin 0.3% eye drops 2.99 USD ml
Aktob 0.3% eye drops 2.85 USD ml
Tobrex 0.3 % Ointment 2.66 USD g
Tobramycin 10 mg/ml 2.26 USD ml
Tobrex 0.3 % Solution 1.88 USD ml
Pms-Tobramycin 0.3 % Solution 1.05 USD ml
Sandoz Tobramycin 0.3 % Solution 1.05 USD ml
Tobramycin 60 mg/50 ml ns 0.19 USD ml
Patents
Country Patent Number Approved Expires
United States 5508269 1994-10-19 2014-10-19
United States 5149694 1992-09-22 2009-09-22
Canada 2414737 2009-01-06 2021-06-26
Properties
State solid
Melting point Not Available
Experimental Properties
Property Value Source
water solubility 1E+003 mg/ml PhysProp
logP -5.8 PhysProp
Predicted Properties
Property Value Source
water solubility 5.37e+01 g/l ALOGPS
logP -2.98 ALOGPS
logP -6.48 ChemAxon Molconvert
logS -0.94 ALOGPS
pKa 13.13 ChemAxon Molconvert
hydrogen acceptor count 14 ChemAxon Molconvert
hydrogen donor count 10 ChemAxon Molconvert
polar surface area 268.17 ChemAxon Molconvert
rotatable bond count 6 ChemAxon Molconvert
refractivity 106.69 ChemAxon Molconvert
polarizability 47.18 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00063 Link_out
KEGG Compound C00397 Link_out
PubChem Compound 36294 Link_out
PubChem Substance 46507662 Link_out
ChemSpider 33377 Link_out
BindingDB 50090265 Link_out
ChEBI 28864 Link_out
ChEMBL 28864 Link_out
Therapeutic Targets Database DAP000110 Link_out
PharmGKB PA451704 Link_out
HET TOY Link_out
Drug Product Database 2241209 Link_out
RxList http://www.rxlist.com/cgi/generic/tobi.htm Link_out
Drugs.com http://www.drugs.com/cdi/tobramycin-drops.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Tobramycin Link_out
ATC Codes
  • J01GB01
  • S01AA12
AHFS Codes
  • 52:04.04
  • 08:12.02
PDB Entries Not Available
FDA label show (413.6 KB)
MSDS show (73.3 KB)
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. 30S ribosomal protein S12

Pharmacological action: yes
Actions: inhibitor

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

Organism class: bacterial
UniProt ID: P0A7S3 Link_out
Gene: rpsL
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  3. 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
  4. Yang G, Trylska J, Tor Y, McCammon JA: Binding of aminoglycosidic antibiotics to the oligonucleotide A-site model and 30S ribosomal subunit: Poisson-Boltzmann model, thermal denaturation, and fluorescence studies. J Med Chem. 2006 Sep 7;49(18):5478-90. Pubmed

2. 16S rRNA

Pharmacological action: unknown
Actions: inhibitor

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.

Gene Sequence: FASTA

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
  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
  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
  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
  5. Chen SY, Lin TH: A molecular dynamics study on binding recognition between several 4,5 and 4,6-linked aminoglycosides with A-site RNA. J Mol Recognit. 2009 Dec 22. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on November 10, 2010 13:41

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.