ETHIONAMIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C8H10N2S
Molecular Weight	166.243
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

CCC1=NC=CC(=C1)C(N)=S

InChI

InChIKey=AEOCXXJPGCBFJA-UHFFFAOYSA-N

InChI=1S/C8H10N2S/c1-2-7-5-6(8(9)11)3-4-10-7/h3-5H,2H2,1H3,(H2,9,11)

HIDE SMILES / InChI

Molecular Formula	C8H10N2S
Molecular Weight	166.243
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description

Ethionamide is a second-line agent, structurally similar to isoniazid, used as a second-line therapy for the treatment of multidrug-resistant tuberculosis or active tuberculosis in case of patient intolerance to other drugs. Depending on its the concentration at the infected site and the susceptibility of the infecting organism it may be bacteriostatic or bactericidal. When used alone rapidly develops bacterial resistance. Ethionamide was approved by FDA in 1965 as TRECATOR manufactured by Wyeth Pharmaceuticals Inc. (purchased by Pfizer in 2009). Ethionamide is specific for Mycobacteria and is thought to exert a toxic effect on mycolic acid components of the bacterial cell wall when activated through intermediate S-oxidation by EtaA. Mycolic acid synthesis was shown to be inhibited by ethionamide in the EthA protein-overexpressing mycobacteria,

CNS Activity

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Catalase-peroxidase 3	Substrate 661
Enoyl-[acyl-carrier-protein] reductase 5	Inhibitor 8,297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Tuberculosis 83	Curative		Approved 8,429	TRECATOR

C_max

Value	Dose	Co-administered	Analyte	Population
2.16 μg/mL	250 mg single, oral		ETHIONAMIDE plasma	Homo sapiens

AUC

Value	Dose	Co-administered	Analyte	Population
7.67 μg × h/mL	250 mg single, oral		ETHIONAMIDE plasma	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.92 h	250 mg single, oral		ETHIONAMIDE plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
70%	250 mg single, oral		ETHIONAMIDE plasma	Homo sapiens

Doses

Doses

Show entries

Dose	Population	Adverse events
0.1 g 2 times / week multiple, oral MTD	unhealthy, >12
0.5 g 2 times / week multiple, oral MTD	unhealthy, >12
0.75 g 2 times / week multiple, oral MTD	unhealthy, >12
1.25 g 2 times / week multiple, oral MTD	unhealthy, >12
1.5 g 2 times / week multiple, oral MTD	unhealthy, >12

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Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1,587	inhibitor 1,767	inhibitor 1,852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1,524 CYP2B6 810 CYP2C8 911 CYP2C19 1,478 BCRP 699 OATP1B1 788

Drug as perpetrator

Show entries

Target	Modality	Activity
CYP2C9 1,819	inhibitor 3,277	no
CYP2D6 1,891	inhibitor 3,277	no
OATP1B1 803	inhibitor 3,277	weak
CYP2C8 965	inhibitor 3,277	yes [IC50 110 uM]
CYP2C19 1,553	inhibitor 3,277	yes [IC50 195 uM]

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Sourcing

Sourcing

Show entries

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:4885	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:4885
ChemicalBook	CB1292374	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB1292374
eMolecules	538116	https://www.emolecules.com/cgi-bin/more?vid=538116
MolPort	MolPort-000-159-777	https://www.molport.com/shop/molecule-link/MolPort-000-159-777
Selleck Chemicals	Ethionamide	http://www.selleckchem.com/products/Ethionamide.html

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PubMed

Show entries

Title	Date	PubMed
Inhibition of testosterone production by propylthiouracil in rat Leydig cells.	2002 Aug	12135875
2-Pyridinethiol/2-pyridinethione tautomeric equilibrium. A comparative experimental and computational study.	2002 Dec 13	12467429
Feasibility and cost-effectiveness of standardised second-line drug treatment for chronic tuberculosis patients: a national cohort study in Peru.	2002 Jun 8	12076553
Drugs that inhibit mycolic acid biosynthesis in Mycobacterium tuberculosis.	2002 Sep	12164478
Diversity in the oxidation of substrates by cytochrome P450 2D6: lack of an obligatory role of aspartate 301-substrate electrostatic bonding.	2002 Sep 10	12206675

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Sample Use Guides

In Vivo Use Guide

15 to 20 mg/kg/day, administered once daily

Route of Administration: Oral

In Vitro Use Guide

Two standardized in vitro susceptibility methods are available for testing ethionamide against M. tuberculosis organisms. The modified proportion method (CDC or NCCLS M24-P) utilizes Middlebrook and Cohn 7H10 agar medium impregnated with ethionamide at a final concentration of 5.0 ug/mL. After 2 to 3 weeks of incubation, MIC99 values are calculated by comparing the quantity of organisms growing in the medium containing drug to the control cultures. Mycobacterial growth in the presence of drug, of at least 1% of the growth in the control culture, indicates resistance.