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Record Information
Version2.0
Creation Date2014-09-11 05:16:08 UTC
Update Date2014-12-24 20:26:57 UTC
Accession NumberT3D4777
Identification
Common NameIsoniazid
ClassSmall Molecule
DescriptionAntibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis.
Compound Type
  • Amide
  • Amine
  • Antitubercular Agent
  • Drug
  • Ester
  • Fatty Acid Synthesis Inhibitor
  • Food Toxin
  • Hydrazine
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
4-pyridinecarbohydrazide
HIA
Hydrazid
Hydrazide
INH
Isohydrazide
Isonicotinhydrazid
Isonicotinic acid hydrazide
Isonicotinic hydrazide
Isonicotinohydrazide
Isonicotinoyl hydrazide
Isonicotinoylhydrazide
Isonicotinsaeurehydrazid
Isonicotinyl hydrazide
Isonicotinyl hydrazine
Isonicotinylhydrazine
Nicozid
Nidrazid
Nydrazid
Pyridine-4-carboxylic acid hydrazide
Rimicid
Rimifon
Servizid
Tibinide
Chemical FormulaC6H7N3O
Average Molecular Mass137.139 g/mol
Monoisotopic Mass137.059 g/mol
CAS Registry Number54-85-3
IUPAC Namepyridine-4-carbohydrazide
Traditional Nameisoniazid
SMILESNNC(=O)C1=CC=NC=C1
InChI IdentifierInChI=1S/C6H7N3O/c7-9-6(10)5-1-3-8-4-2-5/h1-4H,7H2,(H,9,10)
InChI KeyInChIKey=QRXWMOHMRWLFEY-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as pyridinecarboxylic acids and derivatives. Pyridinecarboxylic acids and derivatives are compounds containing a pyridine ring bearing a carboxylic acid group or a derivative thereof.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassPyridines and derivatives
Sub ClassPyridinecarboxylic acids and derivatives
Direct ParentPyridinecarboxylic acids and derivatives
Alternative Parents
Substituents
  • Pyridine carboxylic acid or derivatives
  • Heteroaromatic compound
  • Carboxylic acid hydrazide
  • Azacycle
  • Carboxylic acid derivative
  • Organic nitrogen compound
  • Organic oxygen compound
  • Organopnictogen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point171.4°C
Boiling PointNot Available
Solubility1.4E+005 mg/L (at 25°C)
LogP-0.7
Predicted Properties
PropertyValueSource
Water Solubility34.9 g/LALOGPS
logP-0.71ALOGPS
logP-0.69ChemAxon
logS-0.59ALOGPS
pKa (Strongest Acidic)13.61ChemAxon
pKa (Strongest Basic)3.35ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area68.01 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity37.46 m³·mol⁻¹ChemAxon
Polarizability13.21 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0a4i-2900000000-d379ce585203e68cb06aJSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-000i-0900000000-3cf8f43d0df46334dcd9JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-052r-7900000000-3d43394feacded48669dJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-004i-9000000000-263a0bcadf2e21536983JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-002f-9000000000-17100430370d37f834ceJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-0006-9000000000-9466b9291244c1a61f01JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-000i-0900000000-afcf227eec118bec08a4JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-00di-1900000000-d63af1f463124dbf7b65JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-00fr-9600000000-1d50dedb0eea7ff8dccbJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-004i-9100000000-371fd6d67c48f373e2e5JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-004i-9000000000-dee0012ebd004444b3d8JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000i-0900000000-2900848c5042f3badc64JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-000i-0900000000-aeda0fc92729a2561248JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0zgi-9200000000-8cdf3d4be1d99712a839JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000i-0900000000-0de7d57696bde8b4ad72JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-000i-4900000000-8760bef4d7b9a5b3360cJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-056r-9100000000-7dfda590da30abf9e329JSpectraViewer
MSMass Spectrum (Electron Ionization)splash10-0kdr-9600000000-f04526999a9b68d31861JSpectraViewer | MoNA
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
1D NMR13C NMR SpectrumNot AvailableJSpectraViewer
Toxicity Profile
Route of ExposureReadily absorbed following oral administration; however, may undergo significant first pass metabolism. Absorption and bioavailability are reduced when isoniazid is administered with food.
Mechanism of ToxicityIsoniazid is a prodrug and must be activated by bacterial catalase. Specficially, activation is associated with reduction of the mycobacterial ferric KatG catalase-peroxidase by hydrazine and reaction with oxygen to form an oxyferrous enzyme complex. Once activated, isoniazid inhibits the synthesis of mycoloic acids, an essential component of the bacterial cell wall. At therapeutic levels isoniazid is bacteriocidal against actively growing intracellular and extracellular Mycobacterium tuberculosis organisms. Specifically isoniazid inhibits InhA, the enoyl reductase from Mycobacterium tuberculosis, by forming a covalent adduct with the NAD cofactor. It is the INH-NAD adduct that acts as a slow, tight-binding competitive inhibitor of InhA.
MetabolismPrimarily hepatic. Isoniazid is acetylated by N -acetyl transferase to N -acetylisoniazid; it is then biotransformed to isonicotinic acid and monoacetylhydrazine. Monoacetylhydrazine is associated with hepatotoxicity via formation of a reactive intermediate metabolite when N-hydroxylated by the cytochrome P450 mixed oxidase system. The rate of acetylation is genetically determined. Slow acetylators are characterized by a relative lack of hepatic N -acetyltransferase. Route of Elimination: From 50 to 70 percent of a dose of isoniazid is excreted in the urine within 24 hours. Half Life: Fast acetylators: 0.5 to 1.6 hours. Slow acetylators: 2 to 5 hours.
Toxicity ValuesLD50 100 mg/kg (Human, oral).
Lethal DoseNot Available
Carcinogenicity (IARC Classification)3, not classifiable as to its carcinogenicity to humans. (1)
Uses/SourcesFor the treatment of all forms of tuberculosis in which organisms are susceptible.
Minimum Risk LevelNot Available
Health Effects Adverse reactions include rash, abnormal liver function tests, hepatitis, peripheral neuropathy, mild central nervous system (CNS) effects. In vivo, Isoniazid reacts with pyridoxal to form a hydrazone, and thus inhibits generation of pyridoxal phosphate. Isoniazid also combines with pyridoxal phosphate; high doses interfere with the coenzyme function of the latter.
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00951
HMDB IDHMDB15086
PubChem Compound ID3767
ChEMBL IDCHEMBL64
ChemSpider ID3635
KEGG IDC07054
UniProt IDNot Available
OMIM ID
ChEBI ID6030
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNIZ
ACToR IDNot Available
Wikipedia LinkIsoniazid
References
Synthesis Reference

Costin Rentzea, Albrecht Harreus, Eberhard Ammermann, Gisela Lorenz, “Oxalyl hydrazide-hydroxamic acid derivatives, their preparation and their use as fungicides.” U.S. Patent US5399589, issued November, 1969.

MSDSLink
General References
  1. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Transcription regulatory region dna binding
Specific Function:
Ligand-activated transcriptional activator. Binds to the XRE promoter region of genes it activates. Activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes (such as the CYP1A1 gene). Mediates biochemical and toxic effects of halogenated aromatic hydrocarbons. Involved in cell-cycle regulation. Likely to play an important role in the development and maturation of many tissues. Regulates the circadian clock by inhibiting the basal and circadian expression of the core circadian component PER1. Inhibits PER1 by repressing the CLOCK-ARNTL/BMAL1 heterodimer mediated transcriptional activation of PER1.
Gene Name:
AHR
Uniprot ID:
P35869
Molecular Weight:
96146.705 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.227 uMTox21_AhRTox21/NCGC
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
Gene Name:
CYP2C19
Uniprot ID:
P33261
Molecular Weight:
55930.545 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC501.04 uMNVS_ADME_hCYP2C19Novascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Vitamin d3 25-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 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 (PubMed:11159812). Catalyzes 4-beta-hydroxylation of cholesterol. May catalyze 25-hydroxylation of cholesterol in vitro (PubMed:21576599).
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC501.17 uMNVS_ADME_hCYP3A4Novascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]