Drug Information

Drug (ID: DG01145) and It's Reported Resistant Information

• Name: Perchlozone
• Synonyms: ISONICOTINALDEHYDE THIOSEMICARBAZONE; 4-Formylpyridine thiosemicarbazone; UNII-W2L5NM3ECQ; W2L5NM3ECQ; NSC 731; EINECS 214-848-6; BRN 0132697; perchlozone; Pyridine-4-carboxaldehyde thiosemicarbazone; AI3-52028; pyridine-4-carbaldehyde thiosemicarbazone; [(Z)-pyridin-4-ylmethylideneamino]thiourea; 5-21-07-00360 (Beilstein Handbook Reference); ZINC1587565
• Indication:
  In total 1 Indication(s)
  Multi-drug resistant tuberculosis [ICD-11: MG50-MG52]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Tuberculosis [ICD-11: 1B10]; [1]
• Target: .; NOUNIPROTAC; [1]
• Formula: C7H8N4S
• IsoSMILES: C1=CN=CC=C1/C=N\\NC(=S)N
• InChI: 1S/C7H8N4S/c8-7(12)11-10-5-6-1-3-9-4-2-6/h1-5H,(H3,8,11,12)/b10-5-
• InChIKey: QTSJJDIDTYFLFC-YHYXMXQVSA-N
• PubChem CID: 5374694
• TTD Drug ID: DX7M4S

Type(s) of Resistant Mechanism of This Drug

  DISM: Drug Inactivation by Structure Modification

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-01: Infectious/parasitic diseases

Tuberculosis [ICD-11: 1B10]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

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

• Molecule Alteration: Frameshift mutation; c.106 GA>G
• Resistant Disease: Multidrug-resistant tuberculosis [ICD-11: 1B10.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae strain; 1313
• Experiment for Molecule Alteration: Whole genome sequencing assay
• Mechanism Description: Perchlozone is a prodrug that is activated by EthA and inhibits the HadABC complex.A resistance to perchlozone was shown by in vitro experiments and was mediated by both ethA and hadA mutations.

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

• Molecule Alteration: Frameshift mutation; c.314ACC > ATC (p.Thr > Ile)
• Resistant Disease: Multidrug-resistant tuberculosis [ICD-11: 1B10.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae strain; 1313
• Experiment for Molecule Alteration: Whole genome sequencing assay
• Mechanism Description: Perchlozone is a prodrug that is activated by EthA and inhibits the HadABC complex.A resistance to perchlozone was shown by in vitro experiments and was mediated by both ethA and hadA mutations.

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

• Molecule Alteration: Frameshift mutation; c.702 CT > C
• Resistant Disease: Multidrug-resistant tuberculosis [ICD-11: 1B10.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae strain; 1313
• Experiment for Molecule Alteration: Whole genome sequencing assay
• Mechanism Description: Perchlozone is a prodrug that is activated by EthA and inhibits the HadABC complex.A resistance to perchlozone was shown by in vitro experiments and was mediated by both ethA and hadA mutations.

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

• Molecule Alteration: Frameshift mutation; c.106 GA > G
• Resistant Disease: Multidrug-resistant tuberculosis [ICD-11: 1B10.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae strain; 1313
• Experiment for Molecule Alteration: Whole genome sequencing assay
• Mechanism Description: Perchlozone is a prodrug that is activated by EthA and inhibits the HadABC complex.A resistance to perchlozone was shown by in vitro experiments and was mediated by both ethA and hadA mutations.

Key Molecule: Enoyl-CoA hydratase 2 (HADA) [1]

• Molecule Alteration: Frameshift mutation; c.13CGG > CCC (p.Arg > Pro)
• Resistant Disease: Multidrug-resistant tuberculosis [ICD-11: 1B10.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae strain; 1313
• Experiment for Molecule Alteration: Whole genome sequencing assay
• Mechanism Description: Perchlozone is a prodrug that is activated by EthA and inhibits the HadABC complex.A resistance to perchlozone was shown by in vitro experiments and was mediated by both ethA and hadA mutations.

References

• Ref 1: Genetic Variation Putatively Associated with Mycobacterium tuberculosis Resistance to Perchlozone, a New Thiosemicarbazone: Clues from Whole Genome Sequencing and Implications for Treatment of Multidrug-Resistant Tuberculosis .Antibiotics (Basel). 2020 Oct 3;9(10):669. doi: 10.3390/antibiotics9100669. 10.3390/antibiotics9100669