Tmic
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Record Information
Version2.0
Creation Date2009-07-15 20:47:03 UTC
Update Date2014-12-24 20:25:49 UTC
Accession NumberT3D2675
Identification
Common NameLinezolid
ClassSmall Molecule
DescriptionLinezolid is only found in individuals that have used or taken this drug. It is a synthetic antibiotic, the first of the oxazolidinone class, used for the treatment of infections caused by multi-resistant bacteria including streptococcus and methicillin-resistant Staphylococcus aureus (MRSA). Linezolid is a synthetic antibacterial agent of the oxazolidinone class of antibiotics. It has in vitro activity against aerobic Gram positive bacteria, certain Gram negative bacteria and anaerobic microorganisms. It selectively inhibits bacterial protein synthesis through binding to sites on the bacterial ribosome and prevents the formation of a functional 70S-initiation complex. Specifically, linezolid binds to a site on the bacterial 23S ribosomal RNA of the 50S subunit and prevents the formation of a functional 70S initiation complex, which is an essential component of the bacterial translation process. The results of time-kill studies have shown linezolid to be bacteriostatic against enterococci and staphylococci. For streptococci, linezolid was found to be bactericidal for the majority of strains. Linezolid is also a reversible, nonselective inhibitor of monoamine oxidase. Therefore, linezolid has the potential for interaction with adrenergic and serotonergic agents.
Compound Type
  • Amide
  • Amine
  • Anti-Bacterial Agent
  • Anti-Infective Agent
  • Drug
  • Ester
  • Ether
  • Metabolite
  • Organic Compound
  • Organofluoride
  • Protein Synthesis Inhibitor
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
Antizolid
Linezolide
Linezolidum
Linosept
Linozid
Lizbid
Lizemox
Lizolid
N-(((S)-3-(3-Fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl)methyl)acetamide
Xolid
Zenix
Zizolid
Zodlin
Zolinid
Zyvox
Zyvoxam
Zyvoxid
Chemical FormulaC16H20FN3O4
Average Molecular Mass337.346 g/mol
Monoisotopic Mass337.144 g/mol
CAS Registry Number165800-03-3
IUPAC NameN-{[(5S)-3-[3-fluoro-4-(morpholin-4-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl}acetamide
Traditional Namelinezolid
SMILESCC(=O)NC[C@H]1CN(C(=O)O1)C1=CC(F)=C(C=C1)N1CCOCC1
InChI IdentifierInChI=1S/C16H20FN3O4/c1-11(21)18-9-13-10-20(16(22)24-13)12-2-3-15(14(17)8-12)19-4-6-23-7-5-19/h2-3,8,13H,4-7,9-10H2,1H3,(H,18,21)/t13-/m0/s1
InChI KeyInChIKey=TYZROVQLWOKYKF-ZDUSSCGKSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as phenylmorpholines. These are aromatic compounds containing a morpholine ring and a benzene ring linked to each other through a CC or a CN bond.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassOxazinanes
Sub ClassMorpholines
Direct ParentPhenylmorpholines
Alternative Parents
Substituents
  • Phenylmorpholine
  • Aniline or substituted anilines
  • Tertiary aliphatic/aromatic amine
  • Dialkylarylamine
  • Fluorobenzene
  • Halobenzene
  • Aryl fluoride
  • Aryl halide
  • Monocyclic benzene moiety
  • Oxazolidinone
  • Benzenoid
  • Oxazolidine
  • Acetamide
  • Carbamic acid ester
  • Secondary carboxylic acid amide
  • Tertiary amine
  • Amino acid or derivatives
  • Carboxamide group
  • Carbonic acid derivative
  • Azacycle
  • Oxacycle
  • Carboxylic acid derivative
  • Dialkyl ether
  • Ether
  • Amine
  • Organic oxide
  • Hydrocarbon derivative
  • Organohalogen compound
  • Organofluoride
  • Organonitrogen compound
  • Carbonyl group
  • Organopnictogen compound
  • Organic oxygen compound
  • Organic nitrogen compound
  • Organooxygen compound
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue Locations
  • Bone Marrow
  • Eyes
  • Nerve Cells
PathwaysNot Available
Applications
Biological Roles
Chemical Roles
Physical Properties
StateSolid
AppearanceWhitish crystalline powder (MSDS, A308).
Experimental Properties
PropertyValue
Melting Point182°C
Boiling PointNot Available
Solubility3 mg/mL
LogP0.9
Predicted Properties
PropertyValueSource
Water Solubility1.44 g/LALOGPS
logP0.61ALOGPS
logP0.64ChemAxon
logS-2.4ALOGPS
pKa (Strongest Acidic)14.45ChemAxon
pKa (Strongest Basic)-0.66ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area71.11 ŲChemAxon
Rotatable Bond Count4ChemAxon
Refractivity84.47 m³·mol⁻¹ChemAxon
Polarizability34.06 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0006-4292000000-5170fb56647608eed430View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-000i-0009000000-05a0d0b23e80851df1d5View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-000j-0396000000-959c643931df034e05fcView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-000b-0940000000-066fc762e228726946fbView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0292-0900000000-99847141a31b0134dcfaView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-000j-0900000000-7cf676c358a3890ab460View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-000j-0900000000-fdccf108eb9fcb8a102dView in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-000i-1649000000-a1dedd5c256e9f3bfa4fView in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-000i-0649000000-1ac199ac8af65a2644f8View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000f-0095000000-3ebea74048f88df3cb4aView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0006-0090000000-96eb6763b5a2a907e2f1View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-053r-9860000000-947b5be602b12bd9b78fView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000l-2179000000-12bfdea8c4c5e2b1143eView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0arc-9283000000-ab9a9e6dc95bc68ff6c3View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0btc-9740000000-4ca38bd856baf42e4179View in MoNA
Toxicity Profile
Route of ExposureInhalation (MSDS). Linezolid is rapidly and extensively absorbed after oral dosing. Maximum plasma concentrations are reached approximately 1 to 2 hours after dosing, and the absolute bioavailability is approximately 100%.
Mechanism of ToxicityLinezolid targets the large 39S subunit of the mitochondrial ribosome thereby deactivation mitochondrial protein synthesis. As a result Linezolid is cytotoxic to the most metabolically active cells or tissues including the heart, liver, thymus and bone-marrow. (3). The likely target of Linezolid is the 16S rRNA molecule in the mitochondrial ribosome, which is analogous to the 23S rRNA in bacterial ribosomes.
MetabolismLinezolid is rapidly and extensively absorbed after oral dosing. Maximum plasma concentrations are reached approximately 1 to 2 hours after dosing, and the absolute bioavailability is approximately 100%. Linezolid is primarily metabolized by oxidation of the morpholine ring, which results in two inactive ring-opened carboxylic acid metabolites: the aminoethoxyacetic acid metabolite (A), and the hydroxyethyl glycine metabolite (1). Half Life: 4.5-5.5 hours.
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the treatment of bacterial infections caused by susceptible strains of vancomycin resistant Enterococcus faecium, Staphylococcal aureus (methicillin resistant and susceptible strains), Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae (1).
Minimum Risk LevelNot Available
Health EffectsCommon adverse effects of short-term use include headache, diarrhea, and nausea. Long-term use, however, has been associated with serious adverse effects; linezolid can cause bone marrow suppression and low platelet counts, particularly when used for more than two weeks. If used for longer periods still, it may cause sometimes irreversible chemotherapy-induced peripheral neuropathy and optic nerve damage, and lactic acidosis (a buildup of lactic acid in the body), all most likely due to mitochondrial toxicity.
SymptomsClinical signs of acute toxicity lead to decreased activity, ataxia, vomiting and tremors.
TreatmentDrug therapy is discontinued immediately; exchange transfusion may be required to remove the drug. Sometimes, phenobarbital (UGT induction) is used.
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00601
HMDB IDHMDB14739
PubChem Compound ID441401
ChEMBL IDCHEMBL126
ChemSpider ID390139
KEGG IDC08146
UniProt IDNot Available
OMIM ID
ChEBI ID63607
BioCyc IDNot Available
CTD IDNot Available
Stitch IDLinezolid
PDB IDZLD
ACToR IDNot Available
Wikipedia LinkLinezolid
References
Synthesis Reference

DrugSyn.org

MSDSLink
General References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
  2. Park IN, Hong SB, Oh YM, Kim MN, Lim CM, Lee SD, Koh Y, Kim WS, Kim DS, Kim WD, Shim TS: Efficacy and tolerability of daily-half dose linezolid in patients with intractable multidrug-resistant tuberculosis. J Antimicrob Chemother. 2006 Sep;58(3):701-4. Epub 2006 Jul 19. [16857689 ]
  3. McKee EE, Ferguson M, Bentley AT, Marks TA: Inhibition of mammalian mitochondrial protein synthesis by oxazolidinones. Antimicrob Agents Chemother. 2006 Jun;50(6):2042-9. [16723564 ]
  4. South African Electronic Package Inserts (2001). Zyvoxid. [Link]
  5. Wikipedia. Linezolid. Last updated on 30 July 2014. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Serotonin binding
Specific Function:
Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues. MAOA preferentially oxidizes biogenic amines such as 5-hydroxytryptamine (5-HT), norepinephrine and epinephrine.
Gene Name:
MAOA
Uniprot ID:
P21397
Molecular Weight:
59681.27 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory20 uMNot AvailableBindingDB 50116067
Inhibitory53 uMNot AvailableBindingDB 50116067
Inhibitory55 uMNot AvailableBindingDB 50116067
References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
  2. Hauck SI, Cederberg C, Doucette A, Grosser L, Hales NJ, Poon G, Gravestock MB: New carbon-linked azole oxazolidinones with improved potency and pharmacokinetics. Bioorg Med Chem Lett. 2007 Jan 15;17(2):337-40. Epub 2006 Oct 26. [17095223 ]
  3. Poel TJ, Thomas RC, Adams WJ, Aristoff PA, Barbachyn MR, Boyer FE, Brieland J, Brideau R, Brodfuehrer J, Brown AP, Choy AL, Dermyer M, Dority M, Ford CW, Gadwood RC, Hanna D, Hongliang C, Huband MD, Huber C, Kelly R, Kim JY, Martin JP Jr, Pagano PJ, Ross D, Skerlos L, Sulavik MC, Zhu T, Zurenko GE, Prasad JV: Antibacterial oxazolidinones possessing a novel C-5 side chain. (5R)-trans-3-[3-Fluoro-4- (1-oxotetrahydrothiopyran-4-yl)phenyl]-2- oxooxazolidine-5-carboxylic acid amide (PF-00422602), a new lead compound. J Med Chem. 2007 Nov 29;50(24):5886-9. Epub 2007 Nov 8. [17988109 ]
  4. Brickner SJ, Barbachyn MR, Hutchinson DK, Manninen PR: Linezolid (ZYVOX), the first member of a completely new class of antibacterial agents for treatment of serious gram-positive infections. J Med Chem. 2008 Apr 10;51(7):1981-90. doi: 10.1021/jm800038g. Epub 2008 Mar 14. [18338841 ]
General Function:
Primary amine oxidase activity
Specific Function:
Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues. MAOB preferentially degrades benzylamine and phenylethylamine.
Gene Name:
MAOB
Uniprot ID:
P27338
Molecular Weight:
58762.475 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC5017 uMNot AvailableBindingDB 50116067
References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
  2. Boppana K, Dubey PK, Jagarlapudi SA, Vadivelan S, Rambabu G: Knowledge based identification of MAO-B selective inhibitors using pharmacophore and structure based virtual screening models. Eur J Med Chem. 2009 Sep;44(9):3584-90. doi: 10.1016/j.ejmech.2009.02.031. Epub 2009 Mar 11. [19321235 ]
General Function:
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen. Participates in the bioactivation of carcinogenic aromatic and heterocyclic amines. Catalizes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin.
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular Weight:
58293.76 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC50>20 uMNot AvailableBindingDB 50116067
References
  1. Suzuki H, Utsunomiya I, Shudo K, Fukuhara N, Iwaki T, Yasukata T: Antibacterial oxazolidinone analogues having a N-hydroxyacetyl-substituted seven-membered [1,2,5]triazepane or [1,2,5]oxadiazepane C-ring unit. Eur J Med Chem. 2013 May;63:811-25. doi: 10.1016/j.ejmech.2013.03.003. Epub 2013 Mar 14. [23584544 ]
General Function:
Steroid hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular Weight:
55627.365 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC50>20 uMNot AvailableBindingDB 50116067
References
  1. Suzuki H, Utsunomiya I, Shudo K, Fukuhara N, Iwaki T, Yasukata T: Antibacterial oxazolidinone analogues having a N-hydroxyacetyl-substituted seven-membered [1,2,5]triazepane or [1,2,5]oxadiazepane C-ring unit. Eur J Med Chem. 2013 May;63:811-25. doi: 10.1016/j.ejmech.2013.03.003. Epub 2013 Mar 14. [23584544 ]
General Function:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular Weight:
55768.94 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC50>20 uMNot AvailableBindingDB 50116067
References
  1. Suzuki H, Utsunomiya I, Shudo K, Fukuhara N, Iwaki T, Yasukata T: Antibacterial oxazolidinone analogues having a N-hydroxyacetyl-substituted seven-membered [1,2,5]triazepane or [1,2,5]oxadiazepane C-ring unit. Eur J Med Chem. 2013 May;63:811-25. doi: 10.1016/j.ejmech.2013.03.003. Epub 2013 Mar 14. [23584544 ]
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Binding12.00 uMNot AvailableNot Available