Apramycin

Identification

Summary

Apramycin is an aminoglycoside antibiotic for veterinary use that is used to treat infections in animals.

Generic Name
Apramycin
DrugBank Accession Number
DB04626
Background

Apramycin is an aminoglycoside antibiotic and has a bactericidal action against many gram-negative bacteria. Apramycin is a structurally unique antibiotic that contains a bicyclic sugar moiety and a monosubstituted deoxystreptamine. It is not approved for use in humans.

Type
Small Molecule
Groups
Experimental, Vet approved
Structure
Weight
Average: 539.5771
Monoisotopic: 539.280257179
Chemical Formula
C21H41N5O11
Synonyms
  • 4-O-((8R)-2-amino-8-O-(4-amino-4-deoxy-α-D-glucopyranosyl)-2,3,7-trideoxy-7-(methylamino)-D-glycero-α-D-allo-octodialdo-1,5:8,4-dipyranos-1-yl)-2-deoxy-D-streptamine
  • 4-O-(3α-amino-6α-((4-amino-4-deoxy-α-D-glucopyranosyl)oxy)-2,3,4,5aβ,6,7,8,8aα-octahydro-8β-hydroxy-7β-(methylamino)pyrano(3,2-b)pyran-2α-yl)-2-deoxy-D-streptamine
  • Apramicina
  • Apramycin
  • Apramycine
  • Apramycinum
  • Nebramycin II
External IDs
  • EL-857

Pharmacology

Indication

For the treatment of bacterial infections in animals.

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Contraindications & Blackbox Warnings
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Pharmacodynamics

Not Available

Mechanism of action

Apramycin stands out among aminoglycosides for its mechanism of action which is based on blocking translocation and its ability to bind also to the eukaryotic decoding site despite differences in key residues required for apramycin recognition by the bacterial target. The drug binds in the deep groove of the RNA which forms a continuously stacked helix comprising non-canonical C.A and G.A base pairs and a bulged-out adenine. The binding mode of apramycin at the human decoding-site RNA is distinct from aminoglycoside recognition of the bacterial target, suggesting a molecular basis for the actions of apramycin in eukaryotes and bacteria.

TargetActionsOrganism
U16S ribosomal RNANot AvailableEnteric bacteria and other eubacteria
Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

Not Available

Clearance

Not Available

Adverse Effects
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Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirApramycin may decrease the excretion rate of Abacavir which could result in a higher serum level.
AceclofenacThe risk or severity of nephrotoxicity can be increased when Apramycin is combined with Aceclofenac.
AcemetacinThe risk or severity of nephrotoxicity can be increased when Apramycin is combined with Acemetacin.
AcenocoumarolThe risk or severity of bleeding can be increased when Apramycin is combined with Acenocoumarol.
AcetaminophenApramycin may decrease the excretion rate of Acetaminophen which could result in a higher serum level.
Food Interactions
Not Available

Products

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Product Ingredients
IngredientUNIICASInChI Key
Apramycin sulfate8UYL6NAZ3Q65710-07-8Not applicable

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as aminocyclitol glycosides. These are organic compounds containing an amicocyclitol moiety glycosidically linked to a carbohydrate moiety. There are two major classes of aminoglycosides containing a 2-streptamine core. They are called 4,5- and 4,6-disubstituted 2-deoxystreptamines.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Carbohydrates and carbohydrate conjugates
Direct Parent
Aminocyclitol glycosides
Alternative Parents
Hexoses / Aminocyclitols and derivatives / Cyclohexylamines / Cyclohexanols / Oxanes / 1,3-aminoalcohols / 1,2-aminoalcohols / Oxacyclic compounds / Dialkylamines / Acetals
show 4 more
Substituents
1,2-aminoalcohol / 1,3-aminoalcohol / Acetal / Alcohol / Aliphatic heteropolycyclic compound / Amine / Amino cyclitol glycoside / Aminocyclitol or derivatives / Cyclic alcohol / Cyclitol or derivatives
show 17 more
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
organic heterobicyclic compound, aminoglycoside, 2-deoxystreptamine derivative (CHEBI:2790)
Affected organisms
  • Enteric bacteria and other eubacteria

Chemical Identifiers

UNII
388K3TR36Z
CAS number
37321-09-8
InChI Key
XZNUGFQTQHRASN-XQENGBIVSA-N
InChI
InChI=1S/C21H41N5O11/c1-26-11-14(30)18-8(33-20(11)37-21-16(32)13(29)10(25)9(4-27)34-21)3-7(24)19(36-18)35-17-6(23)2-5(22)12(28)15(17)31/h5-21,26-32H,2-4,22-25H2,1H3/t5-,6+,7-,8+,9-,10-,11+,12+,13+,14-,15-,16-,17-,18+,19+,20-,21-/m1/s1
IUPAC Name
(2R,3R,4S,5S,6S)-2-{[(2R,3S,4R,4aR,6S,7R,8aS)-7-amino-6-{[(1R,2R,3S,4R,6S)-4,6-diamino-2,3-dihydroxycyclohexyl]oxy}-4-hydroxy-3-(methylamino)-octahydropyrano[3,2-b]pyran-2-yl]oxy}-5-amino-6-(hydroxymethyl)oxane-3,4-diol
SMILES
CN[C@H]1[C@@H](O)[C@H]2O[C@H](O[C@@H]3[C@@H](N)C[C@@H](N)[C@H](O)[C@H]3O)[C@H](N)C[C@@H]2O[C@@H]1O[C@H]1O[C@H](CO)[C@@H](N)[C@H](O)[C@H]1O

References

Synthesis Reference

Koji Tomita, Hiroshi Tsukiura, Hiroshi Kawaguchi, "Fermentation process for producing apramycin and nebramycin factor V'." U.S. Patent US4032404, issued December, 1974.

US4032404
General References
  1. Hermann T, Tereshko V, Skripkin E, Patel DJ: Apramycin recognition by the human ribosomal decoding site. Blood Cells Mol Dis. 2007 May-Jun;38(3):193-8. Epub 2007 Jan 29. [Article]
  2. Kondo J, Francois B, Urzhumtsev A, Westhof E: Crystal structure of the Homo sapiens cytoplasmic ribosomal decoding site complexed with apramycin. Angew Chem Int Ed Engl. 2006 May 12;45(20):3310-4. [Article]
  3. Han Q, Zhao Q, Fish S, Simonsen KB, Vourloumis D, Froelich JM, Wall D, Hermann T: Molecular recognition by glycoside pseudo base pairs and triples in an apramycin-RNA complex. Angew Chem Int Ed Engl. 2005 Apr 29;44(18):2694-700. [Article]
KEGG Drug
D02322
KEGG Compound
C01555
PubChem Compound
3081545
PubChem Substance
46509143
ChemSpider
2339128
ChEBI
2790
ChEMBL
CHEMBL1230961
ZINC
ZINC000008214486
Therapeutic Targets Database
DNC000243
PDBe Ligand
AM2
Wikipedia
Apramycin
PDB Entries
1yrj / 2g5k / 2m4q / 2oe5 / 2oe8 / 4aqy / 4k31 / 6mn4 / 7jm2 / 7kes
show 10 more
MSDS
Download (40.6 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceHealthy Volunteers (HV)1
1CompletedTreatmentBacterial Infections1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
PowderOral
Powder, for solutionOral
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
pKa8.5MERCK INDEX (1996)
Predicted Properties
PropertyValueSource
Water Solubility53.3 mg/mLALOGPS
logP-2.8ALOGPS
logP-6.5Chemaxon
logS-1ALOGPS
pKa (Strongest Acidic)12.29Chemaxon
pKa (Strongest Basic)9.53Chemaxon
Physiological Charge5Chemaxon
Hydrogen Acceptor Count16Chemaxon
Hydrogen Donor Count11Chemaxon
Polar Surface Area283.64 Å2Chemaxon
Rotatable Bond Count6Chemaxon
Refractivity120.91 m3·mol-1Chemaxon
Polarizability54.46 Å3Chemaxon
Number of Rings4Chemaxon
Bioavailability0Chemaxon
Rule of FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleYesChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption-0.8007
Blood Brain Barrier-0.9898
Caco-2 permeable-0.7556
P-glycoprotein substrateSubstrate0.568
P-glycoprotein inhibitor INon-inhibitor0.8164
P-glycoprotein inhibitor IINon-inhibitor0.9619
Renal organic cation transporterNon-inhibitor0.885
CYP450 2C9 substrateNon-substrate0.7737
CYP450 2D6 substrateNon-substrate0.8285
CYP450 3A4 substrateNon-substrate0.544
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9196
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.9234
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8708
Ames testAMES toxic0.5193
CarcinogenicityNon-carcinogens0.9671
BiodegradationNot ready biodegradable0.9023
Rat acute toxicity2.2488 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9812
hERG inhibition (predictor II)Non-inhibitor0.8385
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 MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0006-0002090000-bec3afd317316e865944
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-03dl-0309040000-f09f75a8853f489bd6d8
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-000i-0103090000-99def8dff208e2a5e490
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-03xu-7588960000-22d2966628e8bacdd8d9
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-000i-2203690000-1322df877554230c4b00
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4i-5295530000-1758538c03cf56e09a93
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-229.1840904
predicted
DarkChem Lite v0.1.0
[M-H]-219.8899
predicted
DeepCCS 1.0 (2019)
[M+H]+229.4659904
predicted
DarkChem Lite v0.1.0
[M+H]+221.73714
predicted
DeepCCS 1.0 (2019)
[M+Na]+229.6324904
predicted
DarkChem Lite v0.1.0
[M+Na]+227.94258
predicted
DeepCCS 1.0 (2019)

Targets

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Kind
Nucleotide
Organism
Enteric bacteria and other eubacteria
Pharmacological action
Unknown
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.
References
  1. Woodcock J, Moazed D, Cannon M, Davies J, Noller HF: Interaction of antibiotics with A- and P-site-specific bases in 16S ribosomal RNA. EMBO J. 1991 Oct;10(10):3099-103. [Article]
  2. Kondo J, Francois B, Urzhumtsev A, Westhof E: Crystallographic studies of Homo sapiens ribosomal decoding A site complexed with aminoglycosides. Nucleic Acids Symp Ser (Oxf). 2005;(49):253-4. [Article]

Drug created at September 11, 2007 17:49 / Updated at June 12, 2021 10:53