Details of the Drug Combination

General Information of Drug Combination (ID: DCMOGRU)

Drug Combination Name
Linezolid Pyrazinamide
Indication
Disease Entry Status REF
Tuberculosis, Multidrug-Resistant Phase 2 [1]
Component Drugs Linezolid   DMGFPU2 Pyrazinamide   DM4IF32
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 Linezolid
Disease Entry ICD 11 Status REF
Bacteremia 1A73 Approved [2]
Bacterial infection 1A00-1C4Z Approved [3]
Staphylococcal pneumonia N.A. Approved [2]
Staphylococcus aureus infection N.A. Approved [2]
Coronavirus Disease 2019 (COVID-19) 1D6Y Investigative [4]
Skin infection 1F28-1G0Z Investigative [2]
Linezolid Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Bacterial 23S ribosomal RNA (Bact 23S rRNA) TTLFGBV NOUNIPROTAC Binder [7]
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Linezolid Interacts with 2 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Amine oxidase A (MAOA) OT8NIWMQ AOFA_HUMAN Decreases Activity [8]
Amine oxidase B (MAOB) OTTDFM1O AOFB_HUMAN Decreases Activity [8]
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Indication(s) of Pyrazinamide
Disease Entry ICD 11 Status REF
Meningeal tuberculosis N.A. Approved [5]
Mycobacterium infection 1B10-1B21 Approved [6]
Pulmonary tuberculosis 1B10.Z Approved [5]
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 [10]
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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 [11]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [11]
Nicotinamidase (pncA) DERQS6E B0VA03_ACIBY Metabolism [12]
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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 [9]
Eukaryotic translation initiation factor 2 subunit 1 (EIF2S1) OTM0GDTP IF2A_HUMAN Increases Phosphorylation [9]
Endoplasmic reticulum chaperone BiP (HSPA5) OTFUIRAO BIP_HUMAN Increases Expression [9]
Cyclic AMP-dependent transcription factor ATF-4 (ATF4) OTRFV19J ATF4_HUMAN Increases Expression [9]
Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6) OTAFHAVI ATF6A_HUMAN Increases Expression [9]
DNA damage-inducible transcript 3 protein (DDIT3) OTI8YKKE DDIT3_HUMAN Increases Expression [9]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Cleavage [9]
Solute carrier family 22 member 12 (SLC22A12) OT72ZAWS S22AC_HUMAN Affects Activity [13]
Eukaryotic translation initiation factor 2-alpha kinase 3 (EIF2AK3) OT0DZGY4 E2AK3_HUMAN Increases Phosphorylation [9]
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⏷ Show the Full List of 9 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Tuberculosis Multi Drug Resistant Active DCG8UGE N. A. Phase 3 [14]
Tuberculous Meningitis DCXMY9S N. A. Phase 2 [15]
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References

1 ClinicalTrials.gov (NCT02619994) Treatment Shortening of MDR-TB Using Existing and New Drugs
2 Linezolid FDA Label
3 FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (ANDA) 200222.
4 Therapeutic and Triage Strategies for 2019 Novel Coronavirus Disease in Fever Clinics. Lancet Respir Med. 2020 Mar;8(3):e11-e12.
5 Pyrazinamide FDA Label
6 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).
7 Genome sequencing of linezolid-resistant Streptococcus pneumoniae mutants reveals novel mechanisms of resistance. Genome Res. 2009 Jul;19(7):1214-23.
8 Nonclinical Evaluation of Antibacterial Oxazolidinones Contezolid and Contezolid Acefosamil with Low Serotonergic Neurotoxicity. Chem Res Toxicol. 2021 May 17;34(5):1348-1354. doi: 10.1021/acs.chemrestox.0c00524. Epub 2021 Apr 29.
9 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.
10 Pyrazinamide inhibits the eukaryotic-like fatty acid synthetase I (FASI) of Mycobacterium tuberculosis. Nat Med. 2000 Sep;6(9):1043-7.
11 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.
12 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.
13 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.
14 ClinicalTrials.gov (NCT02975570) Efficacy and Tolerability of Delamanid, Linezolid, Pyrazinamide and Levofloxacin
15 ClinicalTrials.gov (NCT05383742) Trial of a Six-Month Regimen of High-Dose Rifampicin, High-Dose Isoniazid, Linezolid, and Pyrazinamide Versus a Standard Nine-Month Regimen for the Treatment of Adults and Adolescents With Tuberculous Meningitis