Drug Information

Drug (ID: DG01184) and It's Reported Resistant Information

• Name: Thiacetazone
• Synonyms: Thiacetazone; Thioacetazone; AMITHIOZONE; Ambathizon; Benzothiozane; Conteben; Benzothiozon; Thiocarbazil; Benthiozone; Thioparamizone; Parazone; Thioacetazon; Thibone; Tibon; Tubin; Siocarbazone; Tebethione; Thiacetone; Thiacetozone; Thioazetazone; Thioparamizon; Thiotebesin; Thiotebezin; Thiotebicina; Tiacetazon; Tioacetazon; Tioatsetazon; Tubercazon; Aktivan; Amitiozon; Berkazon; Domakol; Livazone; Mivizon; Myvizone; Neotibil; Neustab; Novakol; Panrone; Seroden; Tebalon; Tebecure; Tebemar; Tebethion; Tebezon; Thiomicid; Thionicid; Thizone; Tibicur; Tibizan; Tiobicina; Tiocarone; Tiosecolo; Tubigal; Antib; Diasan; Ilbion; Thibon; Tibone; Berculon A; Tebesone I; 104-06-3; Nuclon argentinian; Thiosemicarbarzone; TB I (Bayer); 4-Acetylaminobenzaldehyde thiosemicarbazone; TB I; Thiosemicarbazone; Domagk's T.B.1 conteben; Thioacetazonum; Tibione; 4'-Formylacetanilide thiosemicarbazone; Sdt 1041; Magk's T.B.1 conteben; Tb I/698; p-Acetaminobenzylidenethiosemicarbazone; Tibion; CBC 903150; p-Formylacetanilide-3-thiosemicarbazone; SQ 2321; p-Acetamidobenzaldehyde thiosemicarbazone; p-Acetoaminobenzaldehyde thiosemicarbazone; UNII-MMG78X7SSR; A 4081; 4207 RP; RP 4207; Acetamide, N-[4-[[(aminothioxomethyl)hydrazono]methyl]phenyl]-; p-Acetylaminobenzadehyde thiosemicarbazone; MMG78X7SSR; Acetamide, N-(4-(((aminothioxomethyl)hydrazono)methyl)phenyl)-; NSC3550; Acetanilide, 4'-formyl-, 4'-(thiosemicarbazone); NSC-3550; p-Acetamidobenzaldehyde thiosemicarbazon; NCGC00159389-02; NCGC00159389-03; NCGC00159389-04; p-Acetylaminobenzaldehyde thiosemicarbazone; DSSTox_CID_2593; DSSTox_RID_76650; DSSTox_GSID_22593; N-(4-((2-Carbamothioylhydrazono)methyl)phenyl)acetamide; Mirizone neustab; Tioacetazona; Thioacetazone [INN:BAN]; Thioacetazonum [INN-Latin]; Tioacetazona [INN-Spanish]; CAS-104-06-3; Tb I-698; Thiosemicarbazone (pharmaceutical); NSC 3550; EINECS 203-170-6; BRN 2810335; N-[4-[(E)-(carbamothioylhydrazono)methyl]phenyl]acetamide; N-{4-[(E)-(Carbamothioylhydrazono)methyl]phenyl}acetamide; Citazone; Acetamide, N-(4-(((aminothiomethyl)hydrazono)methylene)phenyl)-; Acetamide, N-[4-[[(aminothiomethyl)hydrazono]methylene]phenyl]-; AI3-18591; 4207RP; Citazone (TN); Acetanilide, 4'-formyl-, thiosemicarbazone; Thioacetazone (INN); SCHEMBL42515; Acetanilide, thiosemicarbazone; WLN: SUYZMNU1R DMV1; 4-14-00-00075 (Beilstein Handbook Reference); N-(4-([2-(Aminocarbothioyl)hydrazono]methyl)phenyl)acetamide; N-[4-[(E)-(carbamothioylhydrazinylidene)methyl]phenyl]acetamide; Acetamide, N1-(4-([2-(aminocarbothioyl)hydrazono]methyl)phenyl); CHEMBL375492; TB-1; Acetamide, N-[4-[[2-(aminothioxomethyl)hydrazinylidene]methyl]phenyl]-; DTXSID80859179; EX-A101; CHEBI:134958; HY-B1526; Tox21_111625; Tox21_111626; Acetanilide, 4'-(thiosemicarbazone); BDBM50247903; MFCD00022157; N-{4-[(E)-(2-carbamothioylhydrazinylidene)methyl]phenyl}acetamide; RP4207; SQ2321; STL503688; ZINC32709513; AKOS000304458; Tox21_111625_1; DB12829; SQ-2321; 4-Acetamidobenzaldehyde thiosemicarbazone; AS-71466; CS-0013329; D08584; A800888; SR-01000872620; SR-01000872620-2; N-{4-[(E)-[(carbamothioylamino)imino]methyl]phenyl}acetamide; N-(4-{(E)-[(aminocarbonothioyl)hydrazono]methyl}phenyl)acetamide; 910379-02-1; N-[4-[(2-Carbamothioylhydrazono)methyl]phenyl]acetamide;N-[4-[(E)-(carbamothioylhydrazono)methyl]phenyl]acetamide
• Indication:
  In total 1 Indication(s)
  Mycobacterium infection [ICD-11: 1B10-1B21]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Validated by in-vivo Model for This Drug (1 diseases)
  Bacterial infection [ICD-11: 1A00-1C4Z]; [1]
• Target: .; NOUNIPROTAC; [1]
• Formula: C10H12N4OS
• IsoSMILES: CC(=O)NC1=CC=C(C=C1)/C=N/NC(=S)N
• InChI: 1S/C10H12N4OS/c1-7(15)13-9-4-2-8(3-5-9)6-12-14-10(11)16/h2-6H,1H3,(H,13,15)(H3,11,14,16)/b12-6+
• InChIKey: SRVJKTDHMYAMHA-WUXMJOGZSA-N
• PubChem CID: 9568512
• ChEBI ID: CHEBI:134958
• TTD Drug ID: D0UF6M
• INTEDE ID: DR2518

Type(s) of Resistant Mechanism of This Drug

  DISM: Drug Inactivation by Structure Modification

  IDUE: Irregularity in Drug Uptake and Drug Efflux

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-01: Infectious/parasitic diseases

Bacterial infection [ICD-11: 1A00-1C4Z]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: FAD-containing monooxygenase EthA (ETHA) [1]

• Molecule Alteration: Expression; Down-regulation
• Resistant Disease: Mycobacterium abscessus infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Mycobacterium abscessus strain CIP104536T; 36809
• In Vitro Model: Mycobacterium bolletii strain CIP108541T; 319705
• In Vitro Model: Mycobacterium massiliense strain CIP108297T; 319705
• Experiment for Molecule Alteration: Whole-genome sequencing assay
• Experiment for Drug Resistance: Microdilution method
• Mechanism Description: TAC, like ethionamide, requires activation by the flavin-containing monooxygenase EthA. EthR, whose gene is adjacent to ethA in M. tuberculosis and in M. smegmatis, represses the transcription of ethA, subsequently preventing the conversion of the prodrugs to active molecules. EthR belongs to the TetR/CamR family of transcriptional regulators that negatively regulates the expression of EthA.

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Siderophore exporter (MMPL5) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Mycobacterium abscessus infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Mycobacterium abscessus strain CIP104536T; 36809
• In Vitro Model: Mycobacterium bolletii strain CIP108541T; 319705
• In Vitro Model: Mycobacterium massiliense strain CIP108297T; 319705
• Experiment for Molecule Alteration: Whole-genome sequencing assay
• Experiment for Drug Resistance: Microdilution method
• Mechanism Description: Importantly, mutations in the transcriptional TetR repressor MAB_4384, with concomitant upregulation of the divergently oriented adjacent genes encoding an MmpS5/MmpL5 efflux pump system, accounted for high cross-resistance levels among all three compounds.

Key Molecule: Siderophore export accessory protein MmpS5 (mmpS5) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Mycobacterium abscessus infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Mycobacterium abscessus strain CIP104536T; 36809
• In Vitro Model: Mycobacterium bolletii strain CIP108541T; 319705
• In Vitro Model: Mycobacterium massiliense strain CIP108297T; 319705
• Experiment for Molecule Alteration: Whole-genome sequencing assay
• Experiment for Drug Resistance: Microdilution method
• Mechanism Description: Importantly, mutations in the transcriptional TetR repressor MAB_4384, with concomitant upregulation of the divergently oriented adjacent genes encoding an MmpS5/MmpL5 efflux pump system, accounted for high cross-resistance levels among all three compounds.

References

• Ref 1: Resistance to Thiacetazone Derivatives Active against Mycobacterium abscessus Involves Mutations in the MmpL5 Transcriptional Repressor MAB_4384 .Antimicrob Agents Chemother. 2017 Mar 24;61(4):e02509-16. doi: 10.1128/AAC.02509-16. Print 2017 Apr. 10.1128/AAC.02509-16