PROTIONAMIDE

Possibly Marketed Outside US

Details

Stereochemistry	ACHIRAL
Molecular Formula	C9H12N2S
Molecular Weight	180.27
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCCC1=NC=CC(=C1)C(N)=S

InChI

InChIKey=VRDIULHPQTYCLN-UHFFFAOYSA-N

InChI=1S/C9H12N2S/c1-2-3-8-6-7(9(10)12)4-5-11-8/h4-6H,2-3H2,1H3,(H2,10,12)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/17227913
Curator's Comment: description was created based on several sources, including http://www.tbonline.info/posts/2011/8/24/prothionamide/ https://www.ncbi.nlm.nih.gov/pubmed/16525107

Protionamide is a thioamide derivative with antitubercular activity, usually involving to treat MDR TB and leprosy. It has the same active substances and cross-resistance with ethionamide. Prothionamide is part of a group of drugs thioamides. The side effects of prothionamide are similar to ethionamide. Prothionamide is most commonly associated with nausea and vomiting. It may cause depression and hallucinations. Rarely, prothionamide will cause jaundice, menstrual disturbances and peripheral neuropathy. Prothionamide has received approval in Germany for the treatment of TB and drug resistant TB. While prothionamide is widely used to treat MDR TB, there is little published evidence demonstrating safety and efficacy. Protionamide forms a covalent adduct with bacterial nicotinamide adenine dinucleotide (NAD), PTH-NAD, which competitively inhibits 2-trans-enoyl-ACP reductase (inhA), an enzyme essential for mycolic acid synthesis. This results in increased cell wall permeability and decreased resistance against cell injury eventually leading to cell lysis. Mycolic acids, long-chain fatty acids, are essential mycobacterial cell wall components and play a key role in resistance to cell injury and mycobacterial virulence.

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
enoyl-acyl ACP reductase, M. leprae 2 Target ID: enoyl-acyl ACP reductase, M. leprae Sources: https://www.ncbi.nlm.nih.gov/pubmed/17227913	Inhibitor 8504
enoyl-acyl ACP reductase, M. tuberculosis 2 Target ID: enoyl-acyl ACP reductase, M. tuberculosis Sources: https://www.ncbi.nlm.nih.gov/pubmed/17227913	Inhibitor 8504

Conditions

Condition	Modality	Highest Phase	Product
Lepromatous leprosy 3 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16525107	Primary	Phase I 438	Unknown Approved Use Unknown
Tuberculous meningitis 2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26586647	Primary	Preclinical	Unknown Approved Use Unknown
Tuberculosis, multidrug-resistant 5 Sources: http://www.tbonline.info/posts/2011/8/24/prothionamide/	Primary	Approved 8583	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
2.5 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19723408/	5.9 mg/kg bw 2 times / day steady-state, oral dose: 5.9 mg/kg bw route of administration: Oral experiment type: STEADY-STATE co-administered:		PROTIONAMIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
1.8 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19723408/	6.5 mg/kg bw 2 times / day steady-state, oral dose: 6.5 mg/kg bw route of administration: Oral experiment type: STEADY-STATE co-administered:		PROTIONAMIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FED

AUC

Value	Dose	Co-administered	Analyte	Population
11.3 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19723408/	5.9 mg/kg bw 2 times / day steady-state, oral dose: 5.9 mg/kg bw route of administration: Oral experiment type: STEADY-STATE co-administered:		PROTIONAMIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
10.4 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19723408/	6.5 mg/kg bw 2 times / day steady-state, oral dose: 6.5 mg/kg bw route of administration: Oral experiment type: STEADY-STATE co-administered:		PROTIONAMIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FED

T_1/2

Value	Dose	Co-administered	Analyte	Population
3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19723408/	5.9 mg/kg bw 2 times / day steady-state, oral dose: 5.9 mg/kg bw route of administration: Oral experiment type: STEADY-STATE co-administered:		PROTIONAMIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
2.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19723408/	6.5 mg/kg bw 2 times / day steady-state, oral dose: 6.5 mg/kg bw route of administration: Oral experiment type: STEADY-STATE co-administered:		PROTIONAMIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FED

Doses

Dose	Population	Adverse events
250 mg 3 times / day multiple, oral Studied dose Dose: 250 mg, 3 times / day Route: oral Route: multiple Dose: 250 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21195892/	unhealthy Health Status: unhealthy Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/21195892/	Disc. AE: Hepatitis... AEs leading to discontinuation/dose reduction: Hepatitis (3 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/21195892/

AEs

AE	Significance	Dose	Population
Hepatitis	3 patients Disc. AE	250 mg 3 times / day multiple, oral Studied dose Dose: 250 mg, 3 times / day Route: oral Route: multiple Dose: 250 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21195892/	unhealthy Health Status: unhealthy Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/21195892/

PubMed

Title	Date	PubMed
Activity of linezolid-containing regimens against multidrug-resistant tuberculosis in mice.	2014-02	24290060
[A study on the activity of clofazimine with antituberculous drugs against Mycobacterium tuberculosis].	2010-09	21092635
[Tuberculosis or sarcoidosis].	2010-03-10	20209770
Disseminated multiorgan MDR-TB resistant to virtually all first-line drugs.	2009-12	20956153
[Effects of two treatment regimens for drug-resistant tuberculosis in tuberculosis control project areas: a comparative study].	2008-12-30	19159566
Extensively drug resistant tuberculosis in a high income country: a report of four unrelated cases.	2008-05-02	18454863
Audiologic monitoring of multi-drug resistant tuberculosis patients on aminoglycoside treatment with long term follow-up.	2007-11-12	17997841
A decade surveillance study of Mycobacterium xenopi disease and antimicrobial susceptibility levels in a reference teaching hospital of northern Italy: HIV-associated versus non-HIV-associated infection.	2004-10-09	15472795
New agents active against Mycobacterium avium complex selected by molecular topology: a virtual screening method.	2004-01	14645324
[Effect of glutoxim in the combination with antitubercular agents of the second choice on the growth of drug resistant Mycobacteria tuberculosis in the cultured murine lung tissue].	2002	12422643
Rapamycin and less immunosuppressive analogs are toxic to Candida albicans and Cryptococcus neoformans via FKBP12-dependent inhibition of TOR.	2001-11	11600372
[Use of the antioxidant ionol to prevent damage to the heart from prolonged administration of antitubercular preparations].	1983-10	6626733

Patents

Sample Use Guides

In Vivo Use Guide

lepromatous leprosy: six times a week at doses of either 250 mg or 500 mg childhood tuberculosis: 15-20 mg/kg with a maximum daily dose of 1000 mg

Route of Administration: Oral

In Vitro Use Guide

Unknown

Name

Type

Language

PROTIONAMIDE

Official Name

English

TREVINTIX

Preferred Name

English

PROTHIONAMIDE [JAN]

Common Name

English

NSC-758962

Code

English

PROTIONAMIDE [MART.]

Common Name

English

PROTIONAMIDE [WHO-IP]

Common Name

English

Protionamide [WHO-DD]

Common Name

English

PROTHIONAMIDE

Common Name

English

RP-9778

Code

English

PROTIONAMIDE [MI]

Common Name

English

2-PROPYLTHIOISONICOTINAMIDE

Systematic Name

English

RP 9778

Code

English

protionamide [INN]

Common Name

English

PROTIONAMIDUM [WHO-IP LATIN]

Common Name

English

TH-1321

Code

English

Classification Tree Code System Code

WHO-ATC

J04AD01