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targets (2)
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Identification
Name Ethionamide
Accession Number DB00609 (APRD00961)
Type small molecule
Groups approved
Description

A second-line antitubercular agent that inhibits mycolic acid synthesis. It also may be used for treatment of leprosy. (From Smith and Reynard, Textbook of Pharmacology, 1992, p868)
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • ET
  • ETH
  • Ethinamide
  • Ethionamid prothionamid
  • Ethionamidum [INN-Latin]
  • Ethioniamide
  • Ethylisothiamide
  • Ethyonomide
  • Etionamid
  • Etionamida [INN-Spanish]
  • Etionamide [DCIT]
  • Etioniamid
  • ETP
Brand names
  • Aethionamidum
  • Aetina
  • Aetiva
  • Amidazin
  • Amidazine
  • Atina
  • Bayer 5312
  • Ethimide
  • Ethina
  • Etimid
  • Etiocidan
  • Etionid
  • Etionizin
  • Etionizina
  • Etionizine
  • Fatoliamid
  • Iridocin
  • Iridozin
  • Isothin
  • Isotiamida
  • Itiocide
  • Nicotion
  • Nisotin
  • Nizotin
  • Rigenicid
  • Sertinon
  • Teberus
  • Thianid
  • Thianide
  • Thioamide
  • Thiomid
  • Thioniden
  • Tianid
  • Tio-Mid
  • Tiomid
  • Trecator
  • Trecator-SC
  • Trekator
  • Trescatyl
  • Trescazide
  • Tubenamide
  • Tubermin
  • Tuberoid
  • Tuberoson
Brand name mixtures Not Available
Categories
  • Leprostatic Agents
  • Antitubercular Agents
  • Fatty Acid Synthesis Inhibitors
CAS number 536-33-4
Weight Average: 166.243
Monoisotopic: 166.056469020
Chemical Formula C8H10N2S
InChI Key InChIKey=AEOCXXJPGCBFJA-UHFFFAOYSA-N
InChI
InChI=1S/C8H10N2S/c1-2-7-5-6(8(9)11)3-4-10-7/h3-5H,2H2,1H3,(H2,9,11)
Plain Text
IUPAC Name
2-ethylpyridine-4-carbothioamide
SMILES
CCC1=NC=CC(=C1)C(N)=S
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Pyridines and Derivatives
Substructures
  • Pyridines and Derivatives
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxylic Acids and Derivatives
  • Imines
Pharmacology
Indication For use in the treatment of pulmonary and extrapulmonary tuberculosis when other antitubercular drugs have failed.
Pharmacodynamics Ethinamate is bacteriostatic against M. tuberculosis. In a study examining ethionamide resistance, ethionamide administered orally initially decreased the number of culturable Mycobacterium tuberculosis organisms from the lungs of H37Rv infected mice. Drug resistance developed with continued ethionamide monotherapy, but did not occur when mice received ethionamide in combination with streptomycin or isoniazid.
Mechanism of action Ethionamide may be bacteriostatic or bactericidal in action, depending on the concentration of the drug attained at the site of infection and the susceptibility of the infecting organism. Ethionamide, like prothionamide and pyrazinamide, is a nicotinic acid derivative related to isoniazid. It is thought that ethionamide undergoes intracellular modification and acts in a similar fashion to isoniazid. Isoniazid inhibits the synthesis of mycoloic acids, an essential component of the bacterial cell wall. 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.
Absorption Essentially completely absorbed following oral administration and not subjected to any appreciable first pass metabolism. Bioavailability approximately 100%.
Volume of distribution
  • 93.5 L [healthy volunteers]
Protein binding Approximately 30% bound to proteins.
Metabolism

Hepatic and extensive. Metabolized to the active metabolite sulfoxide, and several inactive metabolites. The sulphoxide metabolite has been demonstrated to have antimicrobial activity against Mycobacterium tuberculosis.
Route of elimination Less than 1% of the oral dose is excreted as ethionamide in urine. Ethionamide is extensively metabolized to active and inactive metabolites.
Half life 2 to 3 hours
Clearance Not Available
Toxicity Symptoms of overdose include convulsions, nausea, and vomiting.
Affected organisms
  • Mycobacteria
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Wyeth pharmaceuticals inc
Packagers
Dosage forms
Form Route Strength
Tablet, film coated Oral
Prices
Unit description Cost Unit
Trecator 250 mg tablet 4.31 USD tablet
Trecator-SC 250 mg tablet 3.21 USD tablet
Patents Not Available
Properties
State solid
Melting point 163 oC
Experimental Properties
Property Value Source
water solubility Practically insoluble PhysProp
logP 0.5 PhysProp
Predicted Properties
Property Value Source
water solubility 8.39e-01 g/l ALOGPS
logP 1.88 ALOGPS
logP 1.33 ChemAxon Molconvert
logS -2.30 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 1 ChemAxon Molconvert
hydrogen donor count 1 ChemAxon Molconvert
polar surface area 38.91 ChemAxon Molconvert
rotatable bond count 2 ChemAxon Molconvert
refractivity 50.19 ChemAxon Molconvert
polarizability 17.98 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00591 Link_out
KEGG Compound C07665 Link_out
PubChem Compound 2761171 Link_out
PubChem Substance 46506077 Link_out
ChemSpider 2041901 Link_out
ChEBI 4885 Link_out
ChEMBL 4885 Link_out
Therapeutic Targets Database DAP001141 Link_out
PharmGKB PA449528 Link_out
Drug Product Database 0 Link_out
RxList http://www.rxlist.com/cgi/generic2/ethionamide.htm Link_out
Drugs.com http://www.drugs.com/cdi/ethionamide.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Ethionamide Link_out
ATC Codes
  • J04AD03
AHFS Codes Not Available
PDB Entries Not Available
FDA label show (79.3 KB)
MSDS show (50.3 KB)
Interactions
Drug Interactions
Drug Interaction
Food Interactions Not Available
Targets

1. Enoyl-[acyl-carrier-protein] reductase [NADH]

Pharmacological action: yes
Actions: adduct

Involved in the resistance against the antituberculosis drugs isoniazid and ethionamide

Organism class: bacterial
UniProt ID: P0A5Y6 Link_out
Gene: inhA
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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
  2. Morlock GP, Metchock B, Sikes D, Crawford JT, Cooksey RC: ethA, inhA, and katG loci of ethionamide-resistant clinical Mycobacterium tuberculosis isolates. Antimicrob Agents Chemother. 2003 Dec;47(12):3799-805. Pubmed
  3. Banerjee A, Dubnau E, Quemard A, Balasubramanian V, Um KS, Wilson T, Collins D, de Lisle G, Jacobs WR Jr: inhA, a gene encoding a target for isoniazid and ethionamide in Mycobacterium tuberculosis. Science. 1994 Jan 14;263(5144):227-30. Pubmed
  4. Larsen MH, Vilcheze C, Kremer L, Besra GS, Parsons L, Salfinger M, Heifets L, Hazbon MH, Alland D, Sacchettini JC, Jacobs WR Jr: Overexpression of inhA, but not kasA, confers resistance to isoniazid and ethionamide in Mycobacterium smegmatis, M. bovis BCG and M. tuberculosis. Mol Microbiol. 2002 Oct;46(2):453-66. Pubmed
  5. Vilcheze C, Weisbrod TR, Chen B, Kremer L, Hazbon MH, Wang F, Alland D, Sacchettini JC, Jacobs WR Jr: Altered NADH/NAD+ ratio mediates coresistance to isoniazid and ethionamide in mycobacteria. Antimicrob Agents Chemother. 2005 Feb;49(2):708-20. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Peroxidase/catalase T

Pharmacological action: unknown
Actions: other/unknown

Bifunctional, exhibiting both a catalase and broad- spectrum peroxidase activities. May play a role in the intracellular survival of mycobacteria

Organism class: bacterial
UniProt ID: Q08129 Link_out
Gene: katG
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  3. Morlock GP, Metchock B, Sikes D, Crawford JT, Cooksey RC: ethA, inhA, and katG loci of ethionamide-resistant clinical Mycobacterium tuberculosis isolates. Antimicrob Agents Chemother. 2003 Dec;47(12):3799-805. Pubmed
  4. Guo H, Seet Q, Denkin S, Parsons L, Zhang Y: Molecular characterization of isoniazid-resistant clinical isolates of Mycobacterium tuberculosis from the USA. J Med Microbiol. 2006 Nov;55(Pt 11):1527-31. Pubmed
  5. Lavender C, Globan M, Sievers A, Billman-Jacobe H, Fyfe J: Molecular characterization of isoniazid-resistant Mycobacterium tuberculosis isolates collected in Australia. Antimicrob Agents Chemother. 2005 Oct;49(10):4068-74. Pubmed
  6. DeBarber AE, Mdluli K, Bosman M, Bekker LG, Barry CE 3rd: Ethionamide activation and sensitivity in multidrug-resistant Mycobacterium tuberculosis. Proc Natl Acad Sci U S A. 2000 Aug 15;97(17):9677-82. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:05

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.