Drugbank Logo

Showing drug card for Netilmicin (DB00955)

Legend: drug field target field enzyme field

for drugs
Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-02-19 16:03:56
Primary Accession Number DB00955
Secondary Accession Number
  • APRD00232
Name Netilmicin
Drug Type
  • Approved
  • Small Molecule
Description Semisynthetic 1-N-ethyl derivative of sisomycin, an aminoglycoside antibiotic with action similar to gentamicin, but less ear and kidney toxicity. [PubChem]
Synonyms
  1. 1-N-Ethylsisomicin
Brand Names
  1. Netromycin
Brand Mixtures Not Available
Chemical IUPAC Name (2R,3R,4R,5R)-2-[(1S,2S,3R,4S,6R)-4-amino-3-[[(2S,3R)-3-amino-6-(aminomethyl)-3,4-dihydro-2H-pyran-2-yl]oxy]-6-ethylamino-2-hydroxycyclohexyl]oxy-5-methyl-4-methylaminooxane-3,5-diol
Chemical Formula C21H41N5O7
Chemical Structure Structure
CAS Registry Number 56391-56-1
InChI Identifier InChI=1/C21H41N5O7/c1-4-26-13-7-12(24)16(32-19-11(23)6-5-10(8-22)31-19)14(27)17(13)33-20-15(28)18(25-3)21(2,29)9-30-20/h5,11-20,25-29H,4,6-9,22-24H2,1-3H3/t11-,12+,13-,14-,15-,16-,17+,18+,19-,20-,21+/m1/s1
InChI Key CIDUJQMULVCIBT-IULVMANBBU
KEGG Drug Not Available
KEGG Compound C07657 Link Image
PubChem Compound 441306 Link Image
PubChem Substance 9859 Link Image
ChEBI ID 7528 Link Image
PharmGKB ID PA450614 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 00503371 Link Image
RxList Link Not Available
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Netilmicin Link Image
FDA Label Not Available
Material Safety Data Sheet (MSDS)
Synthesis Reference Not Available
Average Molecular Weight 475.5795
Monoisotopic Molecular Weight 475.3006
State Solid
Melting Point Not Available
Experimental Water Solubility 100 mg/mL Source: PhysProp
Predicted Water Solubility 9.20e+00 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity -3 Source: PhysProp
Predicted LogP -1.42 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -1.71 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 1P87 Link Image
Experimental PDB File Show
Experimental PDB Structure
Isomeric SMILES CCN[C@@H]1C[C@H](N)[C@@H](O[C@H]2OC(CN)=CC[C@H]2N)[C@@H](O)[C@H]1O[C@H]1OC[C@](C)(O)[C@@H](NC)[C@H]1O
Canonical SMILES CCNC1CC(N)C(OC2OC(CN)=CCC2N)C(O)C1OC1OCC(C)(O)C(NC)C1O
Drug Category
  • Aminoglycosides
  • Anti-Bacterial Agents
  • Protein Synthesis Inhibitors
ATC Codes
AHFS Codes Not Available
Indication For the treatment of bacteremia, septicaemia, respiratory tract infections, skin and soft-tissue infection, burns, wounds, and peri-operative infections caused by susceptible strains.
Pharmacology Netilmicin is a semisynthetic, water soluble antibiotic of the aminoglycoside group, produced by the fermentation of Micromonospora inyoensis, a species of actinomycete. Aminoglycosides are useful primarily in infections involving aerobic, Gram-negative bacteria, such as Pseudomonas, Acinetobacter, and Enterobacter. It is active at low concentrations against a wide variety of pathogenic bacteria including Escherichia coli, bacteria of the Klebsiella-Enterobacter-Serratia group, Citrobacter sp., Proteus sp. (indole-positive and indole-negative), including Proteus mirabilis, P. morganii, P. rettgrei, P. vulgaris, Pseudomonas aeruginosa and Neisseria gonorrhoea. Netilmicin is also active in vitro against isolates of Hemophilus influenzae, Salmonella sp., Shigella sp. and against penicillinase and non-penicillinase-producing Staphylococcus including methicillin-resistant strains. Some strains of Providencia sp., Acinetobacter sp. and Aeromonas sp. are also sensitive to netilmicin. Many strains of the above organisms which are found to be resistant to other aminoglycosides, such as kanamycin, gentamicin, tobramycin and sisomicin, are susceptible to netilmicin in vitro. Occasionally, strains have been identified which are resistant to amikacin but susceptible to netilmicin. The combination of netilmicin and penicillin G has a synergistic bactericidal effect against most strains of Streptococcus faecalis (enterococcus). The combined effect of netilmicin and carbenicillin or ticarcillin is synergistic for many strains of Pseudomonas aeruginosa. In addition, many isolates of Serratia, which are resistant to multiple antibiotics, are inhibited by synergistic combinations of netilmicin with carbenicillin, azlocillin, mezlocillin, cefamandole, cefotaxime or moxalactam. Aminoglycosides are mostly ineffective against anaerobic bacteria, fungi and viruses.
Mechanism of Action Aminoglycosides like netilmicin "irreversibly" bind to specific 30S-subunit proteins and 16S rRNA. Specifically netilmicin 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, leaving the bacterium unable to synthesize proteins vital to its growth.
Absorption Rapidly and completely absorbed after IM administration, peak serum levels were achieved within 30-60 minutes. Aminoglycosides are poorly absorbed from the gastrointestinal tract.
Toxicity Netilmicin has the potential to cause disturbances in balance and a hearing loss.
Protein Binding Protein-binding of is low and depends on the test conditions (mainly the concentration of cations in the test medium).
Biotransformation No evidence of metabolic transformation, typically 80% is recoverable in the urine within 24 hours
Half Life 2.5 hours
Dosage Forms
Form Route
Solution 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
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
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
Netilmicin Pathway SMP00257 Link Image
General References
  1. Brooks JR, Marlow N, Reeves BC, Millar MR: Use of once-daily netilmicin to treat infants with suspected sepsis in a neonatal intensive care unit. Biol Neonate. 2004;86(3):170-5. Epub 2004 Jun 29. [PubMed Link Image]
  2. Klingenberg C, Smabrekke L, Lier T, Flaegstad T: Validation of a simplified netilmicin dosage regimen in infants. Scand J Infect Dis. 2004;36(6-7):474-9. [PubMed Link Image]
  3. Hemsworth S, Nunn AJ, Selwood K, Osborne C, Jones A, Pizer B: Once-daily netilmicin for neutropenic pyrexia in paediatric oncology. Acta Paediatr. 2005 Mar;94(3):268-74. [PubMed Link Image]
  4. Drugs.com Link Image
  5. http://www.medsafe.govt.nz/profs/Datasheet/n/Netromycininj.htm
  6. Wikipedia 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. Tuuminen T, Heinasmaki T, Kerttula T: First report of bacteremia by Asaia bogorensis, in a patient with a history of intravenous-drug abuse. J Clin Microbiol. 2006 Aug;44(8):3048-50. [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]

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.