Geneticin

Identification

Name
Geneticin
Accession Number
DB04263  (EXPT01586)
Type
Small Molecule
Groups
Experimental
Description

Geneticin (also known as G418) is an aminoglycoside antibiotic similar in structure to gentamicin B1. It is produced by Micromonospora rhodorangea. Geneticin blocks polypeptide synthesis by inhibiting the elongation step in both prokaryotic and eukaryotic cells. Resistance to Geneticin is conferred by the neo gene from Tn5 encoding an aminoglycoside 3‘-phosphotransferase, APH 3‘ II. Geneticin is commonly used in laboratory research to select genetically engineered cells.

Structure
Thumb
Synonyms
Not Available
External IDs
Antibiotic G 418 / Antibiotic g-418 / G-418 / G418
Categories
UNII
A08F5XTI6G
CAS number
49863-47-0
Weight
Average: 496.5524
Monoisotopic: 496.27444352
Chemical Formula
C20H40N4O10
InChI Key
BRZYSWJRSDMWLG-DJWUNRQOSA-N
InChI
InChI=1S/C20H40N4O10/c1-6(25)14-11(27)10(26)9(23)18(32-14)33-15-7(21)4-8(22)16(12(15)28)34-19-13(29)17(24-3)20(2,30)5-31-19/h6-19,24-30H,4-5,21-23H2,1-3H3/t6-,7+,8-,9-,10-,11+,12+,13-,14-,15-,16+,17-,18-,19-,20+/m1/s1
IUPAC Name
(2R,3S,4R,5R,6S)-5-amino-6-{[(1R,2S,3S,4R,6S)-4,6-diamino-3-{[(2R,3R,4R,5R)-3,5-dihydroxy-5-methyl-4-(methylamino)oxan-2-yl]oxy}-2-hydroxycyclohexyl]oxy}-2-[(1R)-1-hydroxyethyl]oxane-3,4-diol
SMILES
[H][C@](C)(O)[C@@]1([H])O[C@]([H])(O[C@]2([H])[C@@]([H])(N)C[C@@]([H])(N)[C@]([H])(O[C@@]3([H])OC[C@](C)(O)[C@]([H])(NC)[C@@]3([H])O)[C@@]2([H])O)[C@]([H])(N)[C@@]([H])(O)[C@]1([H])O

Pharmacology

Indication
Not Available
Pharmacodynamics
Not Available
Mechanism of action
TargetActionsOrganism
UOrnithine decarboxylaseNot AvailableHuman
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
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of bleeding can be increased when Geneticin is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of bleeding can be increased when Geneticin is combined with (S)-Warfarin.
1,10-PhenanthrolineThe therapeutic efficacy of 1,10-Phenanthroline can be decreased when used in combination with Geneticin.
4-hydroxycoumarinThe risk or severity of bleeding can be increased when Geneticin is combined with 4-hydroxycoumarin.
AbacavirGeneticin may decrease the excretion rate of Abacavir which could result in a higher serum level.
AcarboseGeneticin 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 Geneticin.
AcemetacinThe risk or severity of nephrotoxicity can be increased when Acemetacin is combined with Geneticin.
AcenocoumarolThe risk or severity of bleeding can be increased when Geneticin is combined with Acenocoumarol.
AcetaminophenGeneticin may decrease the excretion rate of Acetaminophen which could result in a higher serum level.
Food Interactions
Not Available

References

General References
Not Available
External Links
KEGG Compound
C17703
PubChem Compound
123865
PubChem Substance
46505367
ChemSpider
110402
ChEMBL
CHEMBL215226
HET
GET
Wikipedia
G418
PDB Entries
1mwl / 1njj / 3td1 / 4k32 / 4p3s / 4u4o / 5c4k / 5ndg / 5u18 / 5xz1
show 1 more

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

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

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility58.3 mg/mLALOGPS
logP-2.4ALOGPS
logP-5.3ChemAxon
logS-0.93ALOGPS
pKa (Strongest Acidic)12.42ChemAxon
pKa (Strongest Basic)9.79ChemAxon
Physiological Charge4ChemAxon
Hydrogen Acceptor Count14ChemAxon
Hydrogen Donor Count10ChemAxon
Polar Surface Area248.39 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity114 m3·mol-1ChemAxon
Polarizability50.55 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.9308
Blood Brain Barrier-0.9911
Caco-2 permeable-0.7061
P-glycoprotein substrateSubstrate0.6041
P-glycoprotein inhibitor INon-inhibitor0.6588
P-glycoprotein inhibitor IINon-inhibitor0.9628
Renal organic cation transporterNon-inhibitor0.9159
CYP450 2C9 substrateNon-substrate0.8212
CYP450 2D6 substrateNon-substrate0.8552
CYP450 3A4 substrateSubstrate0.5694
CYP450 1A2 substrateNon-inhibitor0.9021
CYP450 2C9 inhibitorNon-inhibitor0.9028
CYP450 2D6 inhibitorNon-inhibitor0.929
CYP450 2C19 inhibitorNon-inhibitor0.9209
CYP450 3A4 inhibitorNon-inhibitor0.9578
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9114
Ames testNon AMES toxic0.6652
CarcinogenicityNon-carcinogens0.9575
BiodegradationNot ready biodegradable0.9789
Rat acute toxicity1.9026 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9973
hERG inhibition (predictor II)Non-inhibitor0.9179
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/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 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
2-deoxystreptamine aminoglycosides / O-glycosyl compounds / Aminocyclitols and derivatives / Cyclohexylamines / Cyclohexanols / Oxanes / Monosaccharides / Tertiary alcohols / 1,2-aminoalcohols / Oxacyclic compounds
show 5 more
Substituents
Amino cyclitol glycoside / 2-deoxystreptamine aminoglycoside / Glycosyl compound / O-glycosyl compound / Aminocyclitol or derivatives / Cyclohexanol / Cyclohexylamine / Cyclitol or derivatives / Monosaccharide / Oxane
show 18 more
Molecular Framework
Aliphatic heteromonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Protein homodimerization activity
Specific Function
Key enzyme of polyamine biosynthesis that converts ornithine into putrescine, which is the precursor for the polyamines, spermidine and spermine.
Gene Name
ODC1
Uniprot ID
P11926
Uniprot Name
Ornithine decarboxylase
Molecular Weight
51147.73 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. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]

Drug created on June 13, 2005 07:24 / Updated on November 02, 2018 05:54