Details of the Drug Combination

General Information of Drug Combination (ID: DC08G4C)

Drug Combination Name
Pyrazinamide Pretomanid
Indication
Disease Entry Status REF
Pulmonary Tuberculosis Phase 2 [1]
Component Drugs Pyrazinamide   DM4IF32 Pretomanid   DMDYA31
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Pyrazinamide
Disease Entry ICD 11 Status REF
Meningeal tuberculosis N.A. Approved [2]
Mycobacterium infection 1B10-1B21 Approved [3]
Pulmonary tuberculosis 1B10.Z Approved [2]
Pyrazinamide Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Bacterial Fatty acid synthetase I (Bact inhA) TTVTX4N INHA_MYCTU Inhibitor [7]
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Pyrazinamide Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [8]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [8]
Nicotinamidase (pncA) DERQS6E B0VA03_ACIBY Metabolism [9]
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Pyrazinamide Interacts with 9 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1) OTY9R6FZ ERN1_HUMAN Increases Expression [6]
Eukaryotic translation initiation factor 2 subunit 1 (EIF2S1) OTM0GDTP IF2A_HUMAN Increases Phosphorylation [6]
Endoplasmic reticulum chaperone BiP (HSPA5) OTFUIRAO BIP_HUMAN Increases Expression [6]
Cyclic AMP-dependent transcription factor ATF-4 (ATF4) OTRFV19J ATF4_HUMAN Increases Expression [6]
Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6) OTAFHAVI ATF6A_HUMAN Increases Expression [6]
DNA damage-inducible transcript 3 protein (DDIT3) OTI8YKKE DDIT3_HUMAN Increases Expression [6]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Cleavage [6]
Solute carrier family 22 member 12 (SLC22A12) OT72ZAWS S22AC_HUMAN Affects Activity [10]
Eukaryotic translation initiation factor 2-alpha kinase 3 (EIF2AK3) OT0DZGY4 E2AK3_HUMAN Increases Phosphorylation [6]
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⏷ Show the Full List of 9 DOT(s)
Indication(s) of Pretomanid
Disease Entry ICD 11 Status REF
Tuberculosis 1B10-1B14 Approved [4]
Mycobacterium infection 1B10-1B21 Phase 3 [5]
Pretomanid Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Mycobacterium Mycolic acid synthase (MycB cma) TT08ESN CMAS1_MYCTU; CMAS2_MYCTU; CMAS3_MYCTU Inhibitor [4]
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Pretomanid Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [11]
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Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Tuberculosis, Pulmonary, Drug Sensitive DCI1QMJ N. A. Phase 3 [5]
Pulmonary Tuberculosis DCA3OI7 N. A. Phase 1 [12]
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References

1 ClinicalTrials.gov (NCT01498419) Evaluation of 8 Weeks of Treatment With the Combination of Moxifloxacin, PA-824 and Pyrazinamide in Patients With Drug Sensitive and Multi Drug-Resistant Pulmonary Tuberculosis (TB) (NC-002)
2 Pyrazinamide FDA Label
3 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7287).
4 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
5 ClinicalTrials.gov (NCT02342886) Shortening Treatment by Advancing Novel Drugs. U.S. National Institutes of Health.
6 Pyrazinamide-induced hepatotoxicity is alleviated by 4-PBA via inhibition of the PERK-eIF2-ATF4-CHOP pathway. Toxicology. 2017 Mar 1;378:65-75. doi: 10.1016/j.tox.2017.01.002. Epub 2017 Jan 4.
7 Pyrazinamide inhibits the eukaryotic-like fatty acid synthetase I (FASI) of Mycobacterium tuberculosis. Nat Med. 2000 Sep;6(9):1043-7.
8 The metabolism of pyrazoloacridine (NSC 366140) by cytochromes p450 and flavin monooxygenase in human liver microsomes. Clin Cancer Res. 2004 Feb 15;10(4):1471-80.
9 Specificity and mechanism of Acinetobacter baumanii nicotinamidase: implications for activation of the front-line tuberculosis drug pyrazinamide. Angew Chem Int Ed Engl. 2009;48(48):9176-9.
10 Clinical and molecular analysis of patients with renal hypouricemia in Japan-influence of URAT1 gene on urinary urate excretion. J Am Soc Nephrol. 2004 Jan;15(1):164-73. doi: 10.1097/01.asn.0000105320.04395.d0.
11 FDA briefing document - pretomanid tablet, 200 mg meeting of the antimicrobial drugs advisory committee (AMDAC).
12 ClinicalTrials.gov (NCT01215851) Evaluation of Early Bactericidal Activity in Pulmonary Tuberculosis With(J-M-Pa-Z) (NC-001)