Identification

Name
Kanamycin
Accession Number
DB01172  (APRD00026)
Type
Small Molecule
Groups
Approved, Investigational, Vet approved
Description

Kanamycin (also known as kanamycin A) is an aminoglycoside bacteriocidal antibiotic, available in oral, intravenous, and intramuscular forms, and used to treat a wide variety of infections. Kanamycin is isolated from the bacterium Streptomyces kanamyceticus and its most commonly used form is kanamycin sulfate.

Structure
Thumb
Synonyms
  • 4,6-diamino-2-hydroxy-1,3-cyclohexane 3,6'diamino-3,6'-dideoxydi-α-D-glucoside
  • 4,6-diamino-2-hydroxy-1,3-cyclohexylene 3,6'-diamino-3,6'-dideoxydi-D-glucopyranoside
  • Kanamycin A
External IDs
8063-07-8
Product Ingredients
IngredientUNIICASInChI Key
Kanamycin sulfateJ80EX28SMQ25389-94-0OOYGSFOGFJDDHP-KMCOLRRFSA-N
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
KanamycinInjection, solution333 mg/1mLIntramuscular; IntravenousFresenius Kabi2003-01-28Not applicableUs
KantrexInjection, solution1 g/3mLIntramuscular; Intraperitoneal; Intravenous; Irrigation; Respiratory (inhalation)E.R. Squibb & Sons, L.L.C.2005-01-012006-09-30Us
International/Other Brands
Efficin (Lupin) / Kanamytrex (Alcon) / Kancin (Alembic) / Kancin-L (Atlantic) / Kantrex (Merck) / Winamycin (Winston)
Categories
UNII
EQK9Q303C5
CAS number
59-01-8
Weight
Average: 484.4986
Monoisotopic: 484.238058014
Chemical Formula
C18H36N4O11
InChI Key
SBUJHOSQTJFQJX-NOAMYHISSA-N
InChI
InChI=1S/C18H36N4O11/c19-2-6-10(25)12(27)13(28)18(30-6)33-16-5(21)1-4(20)15(14(16)29)32-17-11(26)8(22)9(24)7(3-23)31-17/h4-18,23-29H,1-3,19-22H2/t4-,5+,6-,7-,8+,9-,10-,11-,12+,13-,14-,15+,16-,17-,18-/m1/s1
IUPAC Name
(2R,3S,4S,5R,6R)-2-(aminomethyl)-6-{[(1R,2R,3S,4R,6S)-4,6-diamino-3-{[(2S,3R,4S,5S,6R)-4-amino-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}-2-hydroxycyclohexyl]oxy}oxane-3,4,5-triol
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](O)[C@@H](O)[C@@H]1O

Pharmacology

Indication

For treatment of infections where one or more of the following are the known or suspected pathogens: E. coli, Proteus species (both indole-positive and indole-negative), E. aerogenes, K. pneumoniae, S. marcescens, and Acinetobacter species.

Associated Conditions
Pharmacodynamics

Kanamycin 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 kanamycin "irreversibly" bind to specific 30S-subunit proteins and 16S rRNA. Specifically Kanamycin 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.

TargetActionsOrganism
A30S ribosomal protein S12
inhibitor
Escherichia coli (strain K12)
A16S rRNA
inhibitor
Enteric bacteria and other eubacteria
Absorption

Kanamycin is rapidly absorbed after intramuscular injection and peak serum levels are generally reached within approximately one hour. Poor oral and topical absorption except with severe skin damage.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life

2.5 hours

Clearance
Not Available
Toxicity

Mild and reversible nephrotoxicity may be observed in 5 - 25% of patients. Amikacin accumulates in proximal renal tubular cells. Tubular cell regeneration occurs despite continued drug exposure. Toxicity usually occurs several days following initiation of therapy. May cause irreversible ototoxicity. Otoxocity appears to be correlated to cumulative lifetime exposure. Drug accumulation in the endolymph and perilymph of the inner ear causes irreversible damage to hair cells of the cochlea or summit of ampullar cristae in the vestibular complex. High frequency hearing is lost first with progression leading to loss of low frequency hearing. Further toxicity may lead to retrograde degeneration of the 8th cranial (vestibulocochlear) nerve. Vestibular toxicity may cause vertigo, nausea, vomiting, dizziness and loss of balance. Oral LD50 is 17500 mg/kg in mice, over 4 g/kg in rats, and over 3 g/kg in rabbits.

Affected organisms
  • Enteric bacteria and other eubacteria
Pathways
PathwayCategory
Kanamycin Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(4R)-limonene(4R)-limonene may decrease the excretion rate of Kanamycin which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Kanamycin which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Kanamycin which could result in a higher serum level.
AcetaminophenKanamycin may decrease the excretion rate of Acetaminophen which could result in a higher serum level.
AcetazolamideThe risk or severity of adverse effects can be increased when Acetazolamide is combined with Kanamycin.
AcetyldigitoxinThe serum concentration of Acetyldigitoxin can be decreased when it is combined with Kanamycin.
AcetyldigoxinThe serum concentration of Acetyldigoxin can be decreased when it is combined with Kanamycin.
Acetylsalicylic acidThe risk or severity of nephrotoxicity can be increased when Acetylsalicylic acid is combined with Kanamycin.
AcyclovirKanamycin may decrease the excretion rate of Acyclovir which could result in a higher serum level.
Adefovir DipivoxilThe risk or severity of nephrotoxicity can be increased when Kanamycin is combined with Adefovir Dipivoxil.
Food Interactions
Not Available

References

Synthesis Reference

Hamao Umezawa, Shinichi Kondo, "Method for production of kanamycin C and its derivatives." U.S. Patent US4120955, issued December, 1975.

US4120955
General References
Not Available
External Links
Human Metabolome Database
HMDB0015303
KEGG Compound
C01822
PubChem Compound
6032
PubChem Substance
46508178
ChemSpider
5810
ChEBI
17630
ChEMBL
CHEMBL1384
Therapeutic Targets Database
DNC000201
PharmGKB
PA450137
HET
KAN
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Kanamycin
ATC Codes
A07AA08 — KanamycinJ01GB04 — KanamycinS01AA24 — Kanamycin
PDB Entries
1kny / 1l8t / 1m4i / 1nd4 / 2esi / 3kp5 / 3q5r / 3sg9 / 3u6t / 4dfb
show 13 more
MSDS
Download (71.9 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentOsteomyelitis1
1CompletedOtherTuberculosis1
1CompletedTreatmentHealthy Volunteers1
2, 3RecruitingTreatmentExtensively-drug Resistant Tuberculosis / Tuberculosis / Tuberculosis, Multidrug Resistant1
3CompletedPreventionNeoplasms, Colorectal1
3RecruitingTreatmentMDR-TB1
4RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections1
Not AvailableNot Yet RecruitingPreventionColostomy Stoma / Hirschprung's Disease / Ileostomy - Stoma / Inflammatory Bowel Diseases (IBD) / Intestinal Obstruction / Jejunostomy Stoma / Meconium Ileus / NEC1
Not AvailableRecruitingNot AvailableTuberculosis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • APP Pharmaceuticals
  • Bristol-Myers Squibb Co.
  • Cardinal Health
  • Gallipot
  • Mead Johnson and Co.
Dosage forms
FormRouteStrength
Injection, solutionIntramuscular; Intravenous333 mg/1mL
Injection, solutionIntramuscular; Intraperitoneal; Intravenous; Irrigation; Respiratory (inhalation)1 g/3mL
Prices
Unit descriptionCostUnit
Kanamycin sulfate powder25.2USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP-6.3Not Available
Predicted Properties
PropertyValueSource
Water Solubility92.3 mg/mLALOGPS
logP-3.1ALOGPS
logP-7.1ChemAxon
logS-0.72ALOGPS
pKa (Strongest Acidic)12.11ChemAxon
pKa (Strongest Basic)9.75ChemAxon
Physiological Charge4ChemAxon
Hydrogen Acceptor Count15ChemAxon
Hydrogen Donor Count11ChemAxon
Polar Surface Area282.61 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity106.13 m3·mol-1ChemAxon
Polarizability47.57 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.9351
Blood Brain Barrier-0.9815
Caco-2 permeable-0.7545
P-glycoprotein substrateSubstrate0.5281
P-glycoprotein inhibitor INon-inhibitor0.7592
P-glycoprotein inhibitor IINon-inhibitor0.904
Renal organic cation transporterNon-inhibitor0.8353
CYP450 2C9 substrateNon-substrate0.8325
CYP450 2D6 substrateNon-substrate0.8323
CYP450 3A4 substrateNon-substrate0.6719
CYP450 1A2 substrateNon-inhibitor0.9143
CYP450 2C9 inhibitorNon-inhibitor0.9259
CYP450 2D6 inhibitorNon-inhibitor0.9317
CYP450 2C19 inhibitorNon-inhibitor0.915
CYP450 3A4 inhibitorNon-inhibitor0.97
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9261
Ames testNon AMES toxic0.7406
CarcinogenicityNon-carcinogens0.9488
BiodegradationNot ready biodegradable0.849
Rat acute toxicity1.5431 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9772
hERG inhibition (predictor II)Non-inhibitor0.8151
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
MS/MS Spectrum - DI-ESI-Ion Trap , PositiveLC-MS/MSNot Available
MS/MS Spectrum - DI-ESI-Hybrid FT , PositiveLC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as 4,6-disubstituted 2-deoxystreptamines. These are 2-deoxystreptamine aminoglycosides that a glycosidically linked to a pyranose of furanose unit at the C4- and C6-positions.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Carbohydrates and carbohydrate conjugates
Direct Parent
4,6-disubstituted 2-deoxystreptamines
Alternative Parents
O-glycosyl compounds / Aminocyclitols and derivatives / Cyclohexylamines / Cyclohexanols / Oxanes / Monosaccharides / 1,2-aminoalcohols / Polyols / Oxacyclic compounds / Acetals
show 4 more
Substituents
4,6-disubstituted 2-deoxystreptamine / Glycosyl compound / O-glycosyl compound / Aminocyclitol or derivatives / Cyclohexanol / Cyclohexylamine / Cyclitol or derivatives / Monosaccharide / Oxane / Cyclic alcohol
show 16 more
Molecular Framework
Aliphatic heteromonocyclic compounds
External Descriptors
kanamycins (CHEBI:17630)

Targets

Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Trna binding
Specific Function
With S4 and S5 plays an important role in translational accuracy.Interacts with and stabilizes bases of the 16S rRNA that are involved in tRNA selection in the A site and with the mRNA backbone. Lo...
Gene Name
rpsL
Uniprot ID
P0A7S3
Uniprot Name
30S ribosomal protein S12
Molecular Weight
13736.995 Da
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:17139284]
  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:17016423]
  3. Stavropoulos TA, Strathdee CA: Synergy between tetA and rpsL provides high-stringency positive and negative selection in bacterial artificial chromosome vectors. Genomics. 2001 Feb 15;72(1):99-104. [PubMed:11247671]
  4. Gondo Y, Shioyama Y, Nakao K, Katsuki M: A novel positive detection system of in vivo mutations in rpsL (strA) transgenic mice. Mutat Res. 1996 May 17;360(1):1-14. [PubMed:8657204]
  5. Amanuma K, Takeda H, Amanuma H, Aoki Y: Transgenic zebrafish for detecting mutations caused by compounds in aquatic environments. Nat Biotechnol. 2000 Jan;18(1):62-5. [PubMed:10625393]
2. 16S rRNA
Kind
Nucleotide
Organism
Enteric bacteria and other eubacteria
Pharmacological action
Yes
Actions
Inhibitor
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:17139284]
  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:17016423]
  3. Roy U, Nair D: Biodiversity of organotin resistant Pseudomonas from west coast of India. Ecotoxicology. 2007 Mar;16(2):253-61. Epub 2006 Nov 28. [PubMed:17131180]
  4. Pikuta EV, Hoover RB, Bej AK, Marsic D, Whitman WB, Krader PE, Tang J: Trichococcus patagoniensis sp. nov., a facultative anaerobe that grows at -5 degrees C, isolated from penguin guano in Chilean Patagonia. Int J Syst Evol Microbiol. 2006 Sep;56(Pt 9):2055-62. [PubMed:16957099]
  5. Chung JH, Park YS, Kim J, Shin GW, Nam MH, Oh MK, Kim CW, Jung GY, Hyun Park J: Parallel analysis of antimicrobial activities in microbial community by SSCP based on CE. Electrophoresis. 2007 Jul;28(14):2416-23. [PubMed:17577886]

Enzymes

Kind
Protein
Organism
Mycobacterium tuberculosis
Pharmacological action
Unknown
General Function
May catalyze the coenzyme A-dependent acetylation of the 2' hydroxyl or amino group of a broad spectrum of aminoglycosides and confer resistance to aminoglycosides (By similarity). In vitro assays show no significant increase of resistance to aminoglycosides, possibly due to low expression in a heterologous system (PubMed:9159528).
Specific Function
Aminoglycoside 2'-n-acetyltransferase activity
Gene Name
aac
Uniprot ID
P9WQG9
Uniprot Name
Aminoglycoside 2'-N-acetyltransferase
Molecular Weight
20037.53 Da
References
  1. Vetting MW, Hegde SS, Javid-Majd F, Blanchard JS, Roderick SL: Aminoglycoside 2'-N-acetyltransferase from Mycobacterium tuberculosis in complex with coenzyme A and aminoglycoside substrates. Nat Struct Biol. 2002 Sep;9(9):653-8. [PubMed:12161746]
Kind
Protein
Organism
Staphylococcus aureus
Pharmacological action
Unknown
General Function
Nucleotidyltransferase activity
Specific Function
Inactivates the antibiotic kanamycin by catalyzing the transfer of a nucleotidyl group from nucleoside triphosphates such as ATP to the 4'-hydroxyl group of the aminoglycoside.
Gene Name
knt
Uniprot ID
P05057
Uniprot Name
Kanamycin nucleotidyltransferase
Molecular Weight
28797.38 Da
References
  1. Gates CA, Northrop DB: Substrate specificities and structure-activity relationships for the nucleotidylation of antibiotics catalyzed by aminoglycoside nucleotidyltransferase 2''-I. Biochemistry. 1988 May 17;27(10):3820-5. [PubMed:2841975]
Kind
Protein
Organism
Escherichia coli
Pharmacological action
Unknown
General Function
Kanamycin kinase activity
Specific Function
Resistance to kanamycin and structurally-related aminoglycosides, including amikacin.
Gene Name
aphA1
Uniprot ID
P00551
Uniprot Name
Aminoglycoside 3'-phosphotransferase
Molecular Weight
30960.85 Da
References
  1. Wieninger SA, Serpersu EH, Ullmann GM: ATP binding enables broad antibiotic selectivity of aminoglycoside phosphotransferase(3')-IIIa: an elastic network analysis. J Mol Biol. 2011 Jun 10;409(3):450-65. doi: 10.1016/j.jmb.2011.03.061. Epub 2011 Apr 6. [PubMed:21477597]

Drug created on June 13, 2005 07:24 / Updated on October 01, 2018 16:26