Details
Stereochemistry | ACHIRAL |
Molecular Formula | C23H32N2O2S |
Molecular Weight | 400.577 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CC(C)CCOC1=CC=C(NC(=S)NC2=CC=C(OCCC(C)C)C=C2)C=C1
InChI
InChIKey=BWBONKHPVHMQHE-UHFFFAOYSA-N
InChI=1S/C23H32N2O2S/c1-17(2)13-15-26-21-9-5-19(6-10-21)24-23(28)25-20-7-11-22(12-8-20)27-16-14-18(3)4/h5-12,17-18H,13-16H2,1-4H3,(H2,24,25,28)
Thiocarlide (or tiocarlide or isoxyl) is a drug which was used in the treatment of tuberculosis. In addition was preclinical experiments, which showed, that it purely bacteriostatic against M. leprae. The precise mechanism is still unknown but was shown, that Delta9-desaturase could be a target for it. The more recent experiments have revealed, that Thiocarlide inhibits the dehydration step by the (3R)-hydroxyacyl dehydratases HadAB and HadBC.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
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Target ID: P9WNZ3 Gene ID: 888821.0 Gene Symbol: desA3 Target Organism: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) Sources: https://www.ncbi.nlm.nih.gov/pubmed/14559907 |
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Target ID: HadAB and/or HadBC Sources: https://www.ncbi.nlm.nih.gov/pubmed/23002234 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Curative | Unknown Approved UseUnknown |
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Sources: https://www.ncbi.nlm.nih.gov/pubmed/58847 |
Primary | Unknown Approved UseUnknown |
PubMed
Title | Date | PubMed |
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THE EFFECTIVENESS OF A THIOCARBANILIDE (ISOXYL) AS A THERAPEUTIC DRUG IN MOUSE TUBERCULOSIS. | 1963 Nov |
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Absorption and excretion studies with thiocarlide (4'4-diisoamyloxythiocarbanilide) in man. | 1966 Jun |
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Experimental studies on therapeutic effects of various combinations of antituberculosis drugs. II. Comparison of various regimens in treatment of experimental mouse tuberculosis infected with SM- and INH-resistant Schacht strain. | 1967 Jul |
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[Simultaneous determination of double labelled isoxyl (3H and 35S) blood levels in man, by radio- and bio-assays]. | 1968 |
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[Antitubercular agents. 44. N,N-dialkyldithiooxamide]. | 1988 Nov |
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The use of microarray analysis to determine the gene expression profiles of Mycobacterium tuberculosis in response to anti-bacterial compounds. | 2004 |
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Novel heteroarotinoids as potential antagonists of Mycobacterium bovis BCG. | 2004 Feb 12 |
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A common mechanism of inhibition of the Mycobacterium tuberculosis mycolic acid biosynthetic pathway by isoxyl and thiacetazone. | 2012 Nov 9 |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/5963588
3 g in tablet form (6 tablets of 0.5 g) repeated after six hours.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/14559907
The specific inhibition of oleic acid synthesis by thiocarlide (ISO) suggested that the drug target is the aerobic desaturation system responsible for the synthesis of oleic acid from stearoyl-CoA in mycobacteria. To test this hypothesis Mycobacterium bovis BCG strain was grown in iron-supplemented medium, sonicated, and centrifuged at low speed, and both the cell wall pellet and the supernatant containing both cytosol and plasma membrane were assayed for Δ9 fatty acid desaturase activity. The assay was performed as originally described by Fulco and Bloch with minor modifications. Consistent with the findings of Fulco and Bloch in the absence of NADPH in the assay mixture, no oleic acid was detected. ISO consistently inhibited the incorporation of radioactivity into the oleic acid, but not into stearic acid, by 7% at 0.1 μg/ml and 61% at a concentration of 1.0 μg of ISO/ml in one typical experiment.
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WHO-ATC |
J04AD02
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NCI_THESAURUS |
C280
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WHO-VATC |
QJ04AD02
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43M23X81Y2
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910-86-1
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THIOCARLIDE
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ACTIVE MOIETY