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Identification
NameArbekacin
Accession NumberDB06696
TypeSmall Molecule
GroupsApproved
Description

An semisynthetic aminoglycoside antibiotic. Often used for treatment of multi-resistant bacterial infection such as methicillin-resistant Staphylococcus aureus (MRSA).
Amikacin is also nephrotoxic and ototoxic.

Structure
Thumb
Synonyms
ABK
Arbekacina
Arbekacine
Arbekacinum
Habekacin
Haberacin
External Identifiers
  • 1665-RB
  • AHB-DBK
  • HABA-Dibekacin
  • HABA-DKB
  • HBK
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Arbekacin Sulfate
ThumbNot applicableDBSALT001108
Categories
UNIIG7V6SLI20L
CAS number51025-85-5
WeightAverage: 552.619
Monoisotopic: 552.311891658
Chemical FormulaC22H44N6O10
InChI KeyInChIKey=MKKYBZZTJQGVCD-XTCKQBCOSA-N
InChI
InChI=1S/C22H44N6O10/c23-4-3-12(30)20(34)28-11-5-10(26)18(37-21-9(25)2-1-8(6-24)35-21)17(33)19(11)38-22-16(32)14(27)15(31)13(7-29)36-22/h8-19,21-22,29-33H,1-7,23-27H2,(H,28,34)/t8-,9+,10-,11+,12-,13+,14-,15+,16+,17-,18+,19-,21+,22+/m0/s1
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,6S)-3-amino-6-(aminomethyl)oxan-2-yl]oxy}-3-hydroxycyclohexyl]-2-hydroxybutanamide
SMILES
NCC[[email protected]](O)C(=O)N[C@@H]1C[[email protected]](N)[C@@H](O[[email protected]]2O[[email protected]](CN)CC[[email protected]]2N)[[email protected]](O)[[email protected]]1O[[email protected]]1O[[email protected]](CO)[C@@H](O)[[email protected]](N)[[email protected]]1O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as amino sugars. These are sugars having one alcoholic hydroxy group replaced by an amino group; systematically known as x-amino-x-deoxymonosaccharides. These compounds do not include Glycosylamines.
KingdomOrganic compounds
Super ClassOrganooxygen compounds
ClassCarbohydrates and carbohydrate conjugates
Sub ClassAminosaccharides
Direct ParentAmino sugars
Alternative Parents
Substituents
  • 4,6-disubstituted 2-deoxystreptamine
  • Aminoglycoside core
  • 2-deoxystreptamine aminoglycoside
  • Gamma amino acid or derivatives
  • Glucosamine
  • Amino sugar
  • O-glycosyl compound
  • Glycosyl compound
  • Cyclohexylamine
  • Cyclohexanol
  • Fatty acyl
  • Oxane
  • N-acyl-amine
  • Monosaccharide
  • Fatty amide
  • Cyclic alcohol
  • 1,3-aminoalcohol
  • Secondary carboxylic acid amide
  • Secondary alcohol
  • Carboxamide group
  • 1,2-aminoalcohol
  • Oxacycle
  • Organoheterocyclic compound
  • Carboxylic acid derivative
  • Carboxylic acid amide
  • Acetal
  • Hydrocarbon derivative
  • Primary amine
  • Primary alcohol
  • Organonitrogen compound
  • Primary aliphatic amine
  • Carbonyl group
  • Amine
  • Alcohol
  • Aliphatic heteromonocyclic compound
Molecular FrameworkAliphatic heteromonocyclic compounds
External Descriptors
Pharmacology
IndicationArbekacin is used for the short term treatment of multi-resistant bacterial infections, such as methicillin-resistant Staphylococcus aureus (MRSA).
PharmacodynamicsAminoglycosides, such as Arbekacin, work by binding to the bacterial 30S ribosomal subunit, causing misreading of t-RNA which consequently, leaves the bacterium unable to synthesize proteins vital to its growth. Energy is needed for aminoglycoside uptake into the bacterial cell. Anaerobes have less energy available for this uptake, so aminoglycosides are less active against anaerobes. Aminoglycosides are useful primarily in infections involving aerobic, gram-negative bacteria, such as Pseudomonas, Acinetobacter, and Enterobacter.
Mechanism of actionAminoglycosides, such as Arbekacin, inhibit protein synthesis in susceptible bacteria by irreversibly binding to bacterial 30S and 16S ribosomal subunits. Specifically Arbekacin 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 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.
Related Articles
AbsorptionAminoglycosides are not well absorbed from the gastrointestinal tract. Their absorption is markedly improved by parenteral administration.
Volume of distributionNot Available
Protein binding3-12%
MetabolismNot Available
Route of eliminationNot Available
Half life3 hours
ClearanceNot Available
ToxicityOtotoxicity and nephrotoxicity are the most serious adverse effects of aminoglycoside therapy and are more likely to occur in patients with a history of renal impairment or who are receiving other ototoxic and/or nephrotoxic drugs. Normal duration of IM or IV aminoglycoside therapy is 7-10 days. Although a longer duration may be necessary in some cases, toxicity is more likely to occur when aminoglycoside treatment is continued for longer than 10 days.
Affected organisms
  • Enteric bacteria and other eubacteria
  • Escherichia coli
  • Staphylococcus aureus
  • Acinetobacter
Pathways
PathwayCategorySMPDB ID
Arbekacin Action PathwayDrug actionSMP00713
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.9365
Blood Brain Barrier-0.9659
Caco-2 permeable-0.7588
P-glycoprotein substrateSubstrate0.5786
P-glycoprotein inhibitor INon-inhibitor0.7254
P-glycoprotein inhibitor IINon-inhibitor0.8424
Renal organic cation transporterNon-inhibitor0.8676
CYP450 2C9 substrateNon-substrate0.8204
CYP450 2D6 substrateNon-substrate0.8289
CYP450 3A4 substrateNon-substrate0.559
CYP450 1A2 substrateNon-inhibitor0.933
CYP450 2C9 inhibitorNon-inhibitor0.9392
CYP450 2D6 inhibitorNon-inhibitor0.909
CYP450 2C19 inhibitorNon-inhibitor0.9122
CYP450 3A4 inhibitorNon-inhibitor0.9564
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9002
Ames testNon AMES toxic0.7048
CarcinogenicityNon-carcinogens0.9617
BiodegradationNot ready biodegradable0.6627
Rat acute toxicity1.8593 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9902
hERG inhibition (predictor II)Non-inhibitor0.5444
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point178Not Available
Predicted Properties
PropertyValueSource
Water Solubility41.0 mg/mLALOGPS
logP-2.9ALOGPS
logP-6.9ChemAxon
logS-1.1ALOGPS
pKa (Strongest Acidic)12.49ChemAxon
pKa (Strongest Basic)9.99ChemAxon
Physiological Charge5ChemAxon
Hydrogen Acceptor Count15ChemAxon
Hydrogen Donor Count11ChemAxon
Polar Surface Area297.27 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity129.08 m3·mol-1ChemAxon
Polarizability56.65 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
References
Synthesis Reference

Shinichi Kondo, Seiji Shibahara, Takayuki Usui, Toshiaki Kudo, Shuichi Gomi, Atsushi Tamura, Yoko Ikeda, Daishiro Ikeda, Tomio Takeuchi, “Dibekacin derivatives and arbekacin derivatives active against resistant bacteria, and the production thereof.” U.S. Patent US5618795, issued October, 1989.

US5618795
General References
  1. Inoue M, Nonoyama M, Okamoto R, Ida T: Antimicrobial activity of arbekacin, a new aminoglycoside antibiotic, against methicillin-resistant Staphylococcus aureus. Drugs Exp Clin Res. 1994;20(6):233-9. [PubMed:7758395 ]
  2. Morikawa K, Nonaka M, Yoshikawa Y, Torii I: Synergistic effect of fosfomycin and arbekacin on a methicillin-resistant Staphylococcus aureus-induced biofilm in a rat model. Int J Antimicrob Agents. 2005 Jan;25(1):44-50. [PubMed:15620825 ]
  3. Doi Y, Yokoyama K, Yamane K, Wachino J, Shibata N, Yagi T, Shibayama K, Kato H, Arakawa Y: Plasmid-mediated 16S rRNA methylase in Serratia marcescens conferring high-level resistance to aminoglycosides. Antimicrob Agents Chemother. 2004 Feb;48(2):491-6. [PubMed:14742200 ]
  4. Antimicrobial agents and Chemotherapy [Link]
External Links
ATC CodesJ01GB12
AHFS Codes
  • 08:12.02
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
Alendronic acidArbekacin may increase the activities of Alendronate.
Amphotericin BAmphotericin B may increase the nephrotoxic activities of Arbekacin.
Atracurium besylateArbekacin may increase the activities of Atracurium besylate.
AvibactamAvibactam may increase the nephrotoxic activities of Arbekacin.
Botulinum Toxin Type AArbekacin may increase the neuromuscular blocking activities of Botulinum Toxin Type A.
BumetanideThe risk or severity of adverse effects can be increased when Bumetanide is combined with Arbekacin.
CapreomycinCapreomycin may increase the neuromuscular blocking activities of Arbekacin.
CarboplatinArbekacin may increase the ototoxic activities of Carboplatin.
CefaclorCefaclor may increase the nephrotoxic activities of Arbekacin.
CefdinirCefdinir may increase the nephrotoxic activities of Arbekacin.
CefiximeCefixime may increase the nephrotoxic activities of Arbekacin.
CefotaximeCefotaxime may increase the nephrotoxic activities of Arbekacin.
CefotetanCefotetan may increase the nephrotoxic activities of Arbekacin.
CefoxitinCefoxitin may increase the nephrotoxic activities of Arbekacin.
CefpodoximeCefpodoxime may increase the nephrotoxic activities of Arbekacin.
CefprozilCefprozil may increase the nephrotoxic activities of Arbekacin.
CeftazidimeCeftazidime may increase the nephrotoxic activities of Arbekacin.
CeftibutenCeftibuten may increase the nephrotoxic activities of Arbekacin.
CeftriaxoneCeftriaxone may increase the nephrotoxic activities of Arbekacin.
CefuroximeCefuroxime may increase the nephrotoxic activities of Arbekacin.
CelecoxibCelecoxib may decrease the excretion rate of Arbekacin which could result in a lower serum level and potentially a reduction in efficacy.
Cisatracurium besylateArbekacin may increase the activities of Cisatracurium besylate.
CisplatinCisplatin may increase the nephrotoxic activities of Arbekacin.
ClavulanateThe serum concentration of Arbekacin can be decreased when it is combined with Clavulanate.
ClodronateArbekacin may increase the activities of Clodronate.
ColistimethateArbekacin may increase the nephrotoxic activities of Colistimethate.
ColistinArbekacin may increase the nephrotoxic activities of Colistin.
CyclosporineArbekacin may increase the nephrotoxic activities of Cyclosporine.
DiclofenacDiclofenac may decrease the excretion rate of Arbekacin which could result in a lower serum level and potentially a reduction in efficacy.
DiflunisalDiflunisal may decrease the excretion rate of Arbekacin which could result in a lower serum level and potentially a reduction in efficacy.
DigoxinThe serum concentration of Digoxin can be decreased when it is combined with Arbekacin.
Etacrynic acidThe risk or severity of adverse effects can be increased when Ethacrynic acid is combined with Arbekacin.
EtodolacEtodolac may decrease the excretion rate of Arbekacin which could result in a lower serum level and potentially a reduction in efficacy.
FenoprofenFenoprofen may decrease the excretion rate of Arbekacin which could result in a lower serum level and potentially a reduction in efficacy.
FloctafenineFloctafenine may decrease the excretion rate of Arbekacin which could result in a lower serum level and potentially a reduction in efficacy.
FlurbiprofenFlurbiprofen may decrease the excretion rate of Arbekacin which could result in a lower serum level and potentially a reduction in efficacy.
FoscarnetFoscarnet may increase the nephrotoxic activities of Arbekacin.
FurosemideThe risk or severity of adverse effects can be increased when Furosemide is combined with Arbekacin.
IbandronateArbekacin may increase the activities of Ibandronate.
IbuprofenIbuprofen may decrease the excretion rate of Arbekacin which could result in a lower serum level and potentially a reduction in efficacy.
IndomethacinIndomethacin may decrease the excretion rate of Arbekacin which could result in a lower serum level and potentially a reduction in efficacy.
KetoprofenKetoprofen may decrease the excretion rate of Arbekacin which could result in a lower serum level and potentially a reduction in efficacy.
KetorolacKetorolac may decrease the excretion rate of Arbekacin which could result in a lower serum level and potentially a reduction in efficacy.
MannitolMannitol may increase the nephrotoxic activities of Arbekacin.
MecamylamineArbekacin may increase the neuromuscular blocking activities of Mecamylamine.
Mefenamic acidMefenamic acid may decrease the excretion rate of Arbekacin which could result in a lower serum level and potentially a reduction in efficacy.
MeloxicamMeloxicam may decrease the excretion rate of Arbekacin which could result in a lower serum level and potentially a reduction in efficacy.
NabumetoneNabumetone may decrease the excretion rate of Arbekacin which could result in a lower serum level and potentially a reduction in efficacy.
NaproxenNaproxen may decrease the excretion rate of Arbekacin which could result in a lower serum level and potentially a reduction in efficacy.
OxaprozinOxaprozin may decrease the excretion rate of Arbekacin which could result in a lower serum level and potentially a reduction in efficacy.
PamidronateArbekacin may increase the activities of Pamidronate.
PancuroniumArbekacin may increase the activities of Pancuronium.
PiperacillinThe serum concentration of Arbekacin can be decreased when it is combined with Piperacillin.
PiroxicamPiroxicam may decrease the excretion rate of Arbekacin which could result in a lower serum level and potentially a reduction in efficacy.
RisedronateArbekacin may increase the activities of Risedronate.
RocuroniumArbekacin may increase the activities of Rocuronium.
SuccinylcholineArbekacin may increase the activities of Succinylcholine.
SulindacSulindac may decrease the excretion rate of Arbekacin which could result in a lower serum level and potentially a reduction in efficacy.
TenofovirThe serum concentration of Arbekacin can be increased when it is combined with Tenofovir.
Tiaprofenic acidTiaprofenic acid may decrease the excretion rate of Arbekacin which could result in a lower serum level and potentially a reduction in efficacy.
TicarcillinThe serum concentration of Arbekacin can be decreased when it is combined with Ticarcillin.
TiludronateArbekacin may increase the activities of Tiludronate.
TolmetinTolmetin may decrease the excretion rate of Arbekacin which could result in a lower serum level and potentially a reduction in efficacy.
TorasemideThe risk or severity of adverse effects can be increased when Torasemide is combined with Arbekacin.
VancomycinVancomycin may increase the nephrotoxic activities of Arbekacin.
VecuroniumArbekacin may increase the activities of Vecuronium.
Zoledronic acidArbekacin may increase the activities of Zoledronate.
Food InteractionsNot Available

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. Located at the interface of the 30S and 50S subunits, it traverses the body of the 30S subunit contacting proteins on the other side and probably holding the rRNA structure together. The combined cluste...
Gene Name:
rpsL
Uniprot ID:
P0A7S3
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. 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:320034 ]
  4. Carter AP, Clemons WM, Brodersen DE, Morgan-Warren RJ, Wimberly BT, Ramakrishnan V: Functional insights from the structure of the 30S ribosomal subunit and its interactions with antibiotics. Nature. 2000 Sep 21;407(6802):340-8. [PubMed:11014183 ]
Comments
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Drug created on May 05, 2010 10:31 / Updated on August 17, 2016 12:24