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Showing metabocard for Chlorzoxazone (HMDB0014500)

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IdentificationTaxonomyOntologyPhysical propertiesSpectraBiological propertiesConcentrationsLinksReferencesenzymes (7)transporters (1) Show 8 proteinsXML
enzymes (7)transporters (1) Show 8 proteins
Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:49 UTC
Update Date2020-02-26 21:39:46 UTC
HMDB IDHMDB0014500
Secondary Accession Numbers
  • HMDB14500
Metabolite Identification
Common NameChlorzoxazone
DescriptionChlorzoxazone, also known as paraflex or parafon forte DSC, belongs to the class of organic compounds known as benzoxazolones. These are organic compounds containing a benzene fused to an oxazole ring (a five-member aliphatic ring with three carbon atoms, one oxygen atom, and one nitrogen atom) bearing a ketone group. Chlorzoxazone is a drug which is used for the relief of discomfort associated with acute painful musculoskeletal conditions. Chlorzoxazone is an extremely weak basic (essentially neutral) compound (based on its pKa). Chlorzoxazone may act by inhibiting calcium and potassium influx which would lead to neuronal inhibition and muscle relaxation. The clinical result is a reduction of the skeletal muscle spasm with relief of pain and increased mobility of the involved muscles. Chlorzoxazone inhibits degranulation of mast cells, subsequently preventing the release of histamine and slow-reacting substance of anaphylaxis (SRS-A), mediators of type I allergic reactions. Chlorzoxazone also may reduce the release of inflammatory leukotrienes. Chlorzoxazone is rapidly metabolized in the liver and is excreted in the urine, primarily in a conjugated form as the glucuronide. Chlorzoxazone is a centrally-acting agent for painful musculoskeletal conditions. Oral, mouse: LD50 = 440 mg/kg; Oral, rat: LD50 = 763 mg/kg; Symptoms of overdose include diarrhea, dizziness, drowsiness, headache, light-headedness, nausea, and vomiting.
Structure
Data?1582753186
MOLSDFPDBSMILESInChI
Synonyms
ValueSource
2-Hydroxy-5-chlorobenzoxazoleChEBI
5-Chloro-2(3H)-benzoxazoloneChEBI
5-Chloro-2-benzoxazolinoneChEBI
5-Chloro-2-benzoxazololChEBI
5-Chloro-2-benzoxazoloneChEBI
5-Chloro-2-hydroxybenzoxazoleChEBI
5-ChlorobenzoxazolidoneChEBI
5-Chlorobenzoxazolin-2-oneChEBI
ChlorzoxaneChEBI
ChlorzoxazonaChEBI
ChlorzoxazonumChEBI
ParaflexKegg
ChloroxazoneHMDB
ChlorzoxazonHMDB
McNeil brand OF chlorzoxazoneHMDB
Ortho brand OF chlorzoxazoneHMDB
Parafon forte DSCHMDB
ParafonHMDB
Chemical FormulaC7H4ClNO2
Average Molecular Weight169.565
Monoisotopic Molecular Weight168.993056084
IUPAC Name5-chloro-2,3-dihydro-1,3-benzoxazol-2-one
Traditional Namechlorzoxazone
CAS Registry Number95-25-0
SMILES
ClC1=CC2=C(OC(=O)N2)C=C1
InChI Identifier
InChI=1S/C7H4ClNO2/c8-4-1-2-6-5(3-4)9-7(10)11-6/h1-3H,(H,9,10)
InChI KeyTZFWDZFKRBELIQ-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as benzoxazolones. These are organic compounds containing a benzene fused to an oxazole ring (a five-member aliphatic ring with three carbon atoms, one oxygen atom, and one nitrogen atom) bearing a ketone group.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzoxazoles
Sub ClassBenzoxazolones
Direct ParentBenzoxazolones
Alternative Parents
Substituents
  • Benzoxazolone
  • Aryl chloride
  • Aryl halide
  • Benzenoid
  • Azole
  • Oxazole
  • Heteroaromatic compound
  • Azacycle
  • Oxacycle
  • Organic oxide
  • Organic nitrogen compound
  • Organooxygen compound
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Organopnictogen compound
  • Organic oxygen compound
  • Hydrocarbon derivative
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
Disposition

Biological location:

Role

Industrial application:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point191.5 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility2.96 g/LNot Available
LogP1.6Not Available
Predicted Properties
PropertyValueSource
Water Solubility2.96 g/LALOGPS
logP2.09ALOGPS
logP1.94ChemAxon
logS-1.8ALOGPS
pKa (Strongest Acidic)9.39ChemAxon
pKa (Strongest Basic)-2.2ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area38.33 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity41.07 m³·mol⁻¹ChemAxon
Polarizability14.94 ųChemAxon
Number of Rings2ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectrum TypeDescriptionSplash KeyView
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-02t9-7900000000-bf1beeca5227a276a1a9Spectrum
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-02t9-7900000000-bf1beeca5227a276a1a9Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-014i-1900000000-77df83a0769511baeb96Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-00di-0900000000-60a947f3a3a65702c43bSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-014i-0900000000-5049b81b3f21c5158973Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-014i-0900000000-c7ee77e191a097d4e0baSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-00lr-0900000000-004a71f655e522e841deSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-001i-4900000000-b7b03cbc9d434e2b03f2Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-003i-9100000000-8a0cf328f650c7cd4780Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-00di-0900000000-60a947f3a3a65702c43bSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00di-0900000000-b157f14bda84940ce6f0Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00di-0900000000-1160c69f5a00e22b993dSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-001i-0900000000-4ad343b03b4421d4d5efSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-014i-0900000000-8f6b0f1e098737ec9a8bSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-014i-0900000000-77cf5afa849168e0d47cSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-001l-2900000000-4530cefc3528a1ea69aaSpectrum
Biological Properties
Cellular Locations
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00356 details
UrineExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00356 details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00356
Phenol Explorer Compound IDNot Available
FooDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID2632
KEGG Compound IDC07931
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkChlorzoxazone
METLIN IDNot Available
PubChem Compound2733
PDB IDCLW
ChEBI ID3655
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB ID
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Wan J, Ernstgard L, Song BJ, Shoaf SE: Chlorzoxazone metabolism is increased in fasted Sprague-Dawley rats. J Pharm Pharmacol. 2006 Jan;58(1):51-61. [PubMed:16393464 ]
  2. Park JY, Kim KA, Park PW, Ha JM: Effect of high-dose aspirin on CYP2E1 activity in healthy subjects measured using chlorzoxazone as a probe. J Clin Pharmacol. 2006 Jan;46(1):109-14. [PubMed:16397290 ]
  3. Dong DL, Luan Y, Feng TM, Fan CL, Yue P, Sun ZJ, Gu RM, Yang BF: Chlorzoxazone inhibits contraction of rat thoracic aorta. Eur J Pharmacol. 2006 Sep 18;545(2-3):161-6. Epub 2006 Jun 29. [PubMed:16859676 ]

Enzymes

Enzyme Details
1. Cytochrome P450 3A4
General function:
Involved in monooxygenase 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 performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular weight:
57255.585
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Enzyme Details
2. Cytochrome P450 2E1
General function:
Involved in monooxygenase activity
Specific function:
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic or carcinogenic forms.
Gene Name:
CYP2E1
Uniprot ID:
P05181
Molecular weight:
56848.42
References
  1. Pelkonen O, Maenpaa J, Taavitsainen P, Rautio A, Raunio H: Inhibition and induction of human cytochrome P450 (CYP) enzymes. Xenobiotica. 1998 Dec;28(12):1203-53. [PubMed:9890159 ]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
  3. Yasar U, Forslund-Bergengren C, Tybring G, Dorado P, Llerena A, Sjoqvist F, Eliasson E, Dahl ML: Pharmacokinetics of losartan and its metabolite E-3174 in relation to the CYP2C9 genotype. Clin Pharmacol Ther. 2002 Jan;71(1):89-98. [PubMed:11823761 ]
Enzyme Details
3. Cytochrome P450 2D6
General function:
Involved in monooxygenase 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
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Enzyme Details
4. Cytochrome P450 1A1
General function:
Involved in monooxygenase 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.
Gene Name:
CYP1A1
Uniprot ID:
P04798
Molecular weight:
58164.815
References
  1. Wiercinska P, Squires EJ: Chlorzoxazone metabolism by porcine cytochrome P450 enzymes and the effect of cytochrome b5. Drug Metab Dispos. 2010 May;38(5):857-62. doi: 10.1124/dmd.109.030528. Epub 2010 Feb 17. [PubMed:20164110 ]
  2. Warrington JS, Court MH, Greenblatt DJ, von Moltke LL: Phenacetin and chlorzoxazone biotransformation in aging male Fischer 344 rats. J Pharm Pharmacol. 2004 Jun;56(6):819-25. [PubMed:15231049 ]
Enzyme Details
5. Cytochrome P450 1A2
General function:
Involved in monooxygenase 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. 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:
58406.915
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Enzyme Details
6. Cytochrome P450 2A6
General function:
Involved in monooxygenase activity
Specific function:
Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Constitutes the major nicotine C-oxidase. Acts as a 1,4-cineole 2-exo-monooxygenase. Possesses low phenacetin O-deethylation activity.
Gene Name:
CYP2A6
Uniprot ID:
P11509
Molecular weight:
56517.005
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Enzyme Details
7. Calcium-activated potassium channel subunit alpha-1
General function:
Involved in ion channel activity
Specific function:
Potassium channel activated by both membrane depolarization or increase in cytosolic Ca(2+) that mediates export of K(+). It is also activated by the concentration of cytosolic Mg(2+). Its activation dampens the excitatory events that elevate the cytosolic Ca(2+) concentration and/or depolarize the cell membrane. It therefore contributes to repolarization of the membrane potential. Plays a key role in controlling excitability in a number of systems, such as regulation of the contraction of smooth muscle, the tuning of hair cells in the cochlea, regulation of transmitter release, and innate immunity. In smooth muscles, its activation by high level of Ca(2+), caused by ryanodine receptors in the sarcoplasmic reticulum, regulates the membrane potential. In cochlea cells, its number and kinetic properties partly determine the characteristic frequency of each hair cell and thereby helps to establish a tonotopic map. Kinetics of KCNMA1 channels are determined by alternative splicing, phosphorylation status and its combination with modulating beta subunits. Highly sensitive to both iberiotoxin (IbTx) and charybdotoxin (CTX)
Gene Name:
KCNMA1
Uniprot ID:
Q12791
Molecular weight:
137558.1
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. Dong DL, Luan Y, Feng TM, Fan CL, Yue P, Sun ZJ, Gu RM, Yang BF: Chlorzoxazone inhibits contraction of rat thoracic aorta. Eur J Pharmacol. 2006 Sep 18;545(2-3):161-6. Epub 2006 Jun 29. [PubMed:16859676 ]
  4. Alvina K, Khodakhah K: KCa channels as therapeutic targets in episodic ataxia type-2. J Neurosci. 2010 May 26;30(21):7249-57. doi: 10.1523/JNEUROSCI.6341-09.2010. [PubMed:20505091 ]
  5. Syme CA, Gerlach AC, Singh AK, Devor DC: Pharmacological activation of cloned intermediate- and small-conductance Ca(2+)-activated K(+) channels. Am J Physiol Cell Physiol. 2000 Mar;278(3):C570-81. [PubMed:10712246 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]

Transporters

Enzyme Details
1. Multidrug resistance protein 1
General function:
Involved in ATP binding
Specific function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular weight:
141477.3
References
  1. Kim RB, Wandel C, Leake B, Cvetkovic M, Fromm MF, Dempsey PJ, Roden MM, Belas F, Chaudhary AK, Roden DM, Wood AJ, Wilkinson GR: Interrelationship between substrates and inhibitors of human CYP3A and P-glycoprotein. Pharm Res. 1999 Mar;16(3):408-14. [PubMed:10213372 ]