Identification

Name
Arbekacin
Accession Number
DB06696
Type
Small Molecule
Groups
Experimental, Investigational
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 IDs
1665-RB / AHB-DBK / HABA-Dibekacin / HABA-DKB / HBK / ME-1100 / ME1100
Product Ingredients
IngredientUNIICASInChI Key
Arbekacin SulfateG7395HZ992104931-87-5UTUVRPOLEMRKQC-XDJMXTNXSA-N
Categories
UNII
G7V6SLI20L
CAS number
51025-85-5
Weight
Average: 552.619
Monoisotopic: 552.311891658
Chemical Formula
C22H44N6O10
InChI Key
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[C@H](O)C(=O)N[C@@H]1C[C@H](N)[C@@H](O[C@H]2O[C@H](CN)CC[C@H]2N)[C@H](O)[C@H]1O[C@H]1O[C@H](CO)[C@@H](O)[C@H](N)[C@H]1O

Pharmacology

Indication

Arbekacin is used for the short term treatment of multi-resistant bacterial infections, such as methicillin-resistant Staphylococcus aureus (MRSA).

Pharmacodynamics

Aminoglycosides, 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 action

Aminoglycosides, 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.

TargetActionsOrganism
A30S ribosomal protein S12
inhibitor
Escherichia coli (strain K12)
Absorption

Aminoglycosides are not well absorbed from the gastrointestinal tract. Their absorption is markedly improved by parenteral administration.

Volume of distribution
Not Available
Protein binding

3-12%

Metabolism
Not Available
Route of elimination
Not Available
Half life

3 hours

Clearance
Not Available
Toxicity

Ototoxicity 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
PathwayCategory
Arbekacin Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of bleeding can be increased when Arbekacin is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of bleeding can be increased when Arbekacin is combined with (S)-Warfarin.
1,10-PhenanthrolineThe therapeutic efficacy of 1,10-Phenanthroline can be decreased when used in combination with Arbekacin.
4-hydroxycoumarinThe risk or severity of bleeding can be increased when Arbekacin is combined with 4-hydroxycoumarin.
AbacavirArbekacin may decrease the excretion rate of Abacavir which could result in a higher serum level.
AcarboseArbekacin may decrease the excretion rate of Acarbose which could result in a higher serum level.
AceclofenacThe risk or severity of nephrotoxicity can be increased when Aceclofenac is combined with Arbekacin.
AcemetacinThe risk or severity of nephrotoxicity can be increased when Acemetacin is combined with Arbekacin.
AcenocoumarolThe risk or severity of bleeding can be increased when Arbekacin is combined with Acenocoumarol.
AcetaminophenArbekacin may decrease the excretion rate of Acetaminophen which could result in a higher serum level.
Food Interactions
Not 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
Human Metabolome Database
HMDB0015642
KEGG Drug
D07462
PubChem Compound
68682
PubChem Substance
99443250
ChemSpider
61936
ChEBI
37922
ChEMBL
CHEMBL426926
PharmGKB
PA165958370
HET
84G
Drugs.com
Drugs.com Drug Page
Wikipedia
Arbekacin
ATC Codes
J01GB12 — Arbekacin
PDB Entries
6cgg

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentHealthy Volunteers2
2Active Not RecruitingTreatmentMuscular Dystrophy, Duchenne1
Not AvailableNo Longer AvailableNot AvailableInfection Due to Resistant Organism1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)178Not 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 FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
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)

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

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 / Cyclohexanols / Cyclohexylamines / Oxanes / Monosaccharides / 1,3-aminoalcohols / 1,2-aminoalcohols / Propargyl-type 1,3-dipolar organic compounds / Acetals
show 6 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 20 more
Molecular Framework
Aliphatic heteromonocyclic compounds
External Descriptors
aminoglycoside, kanamycins (CHEBI:37922)

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. 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]

Drug created on May 05, 2010 10:31 / Updated on November 02, 2018 08:46