Details of the Drug Combination

General Information of Drug Combination (ID: DCGTTEP)

Drug Combination Name
Pyrazinamide Clofazimine
Indication
Disease Entry Status REF
Tuberculosis, Multidrug-Resistant Phase 3 [1]
Component Drugs Pyrazinamide   DM4IF32 Clofazimine   DMEBOFW
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 [8]
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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 [9]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [9]
Nicotinamidase (pncA) DERQS6E B0VA03_ACIBY Metabolism [10]
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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 [7]
Eukaryotic translation initiation factor 2 subunit 1 (EIF2S1) OTM0GDTP IF2A_HUMAN Increases Phosphorylation [7]
Endoplasmic reticulum chaperone BiP (HSPA5) OTFUIRAO BIP_HUMAN Increases Expression [7]
Cyclic AMP-dependent transcription factor ATF-4 (ATF4) OTRFV19J ATF4_HUMAN Increases Expression [7]
Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6) OTAFHAVI ATF6A_HUMAN Increases Expression [7]
DNA damage-inducible transcript 3 protein (DDIT3) OTI8YKKE DDIT3_HUMAN Increases Expression [7]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Cleavage [7]
Solute carrier family 22 member 12 (SLC22A12) OT72ZAWS S22AC_HUMAN Affects Activity [11]
Eukaryotic translation initiation factor 2-alpha kinase 3 (EIF2AK3) OT0DZGY4 E2AK3_HUMAN Increases Phosphorylation [7]
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⏷ Show the Full List of 9 DOT(s)
Indication(s) of Clofazimine
Disease Entry ICD 11 Status REF
Crohn disease DD70 Approved [4]
Leprosy N.A. Approved [5]
Multibacillary leprosy N.A. Approved [5]
Pyoderma gangrenosum EB21 Approved [5]
Mycobacterium infection 1B10-1B21 Investigative [6]
Clofazimine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Bacterial Deoxyribonucleic acid (Bact DNA) TTS1W4A NOUNIPROTAC Modulator [12]
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Clofazimine Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [13]
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Clofazimine Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [14]
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Clofazimine Interacts with 2 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [15]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [16]
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References

1 ClinicalTrials.gov (NCT02754765) Evaluating Newly Approved Drugs for Multidrug-resistant TB
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 FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 019500.
5 Clofazimine FDA Label
6 The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
7 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.
8 Pyrazinamide inhibits the eukaryotic-like fatty acid synthetase I (FASI) of Mycobacterium tuberculosis. Nat Med. 2000 Sep;6(9):1043-7.
9 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.
10 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.
11 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.
12 The mode of action of clofazimine DNA binding studies. Int J Lepr Other Mycobact Dis. 1976 Jan-Jun;44(1-2):133-4.
13 Efflux pump inhibitors: targeting mycobacterial efflux systems to enhance TB therapy. J Antimicrob Chemother. 2016 Jan;71(1):17-26.
14 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
15 Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development. Toxicol Sci. 2010 Dec; 118(2):485-500.
16 Why are most phospholipidosis inducers also hERG blockers?. Arch Toxicol. 2017 Dec;91(12):3885-3895. doi: 10.1007/s00204-017-1995-9. Epub 2017 May 27.