Details of the Drug Combination

General Information of Drug Combination (ID: DCJ20NX)

Drug Combination Name
Pyrazinamide Celecoxib
Indication
Disease Entry Status REF
Tuberculosis Phase 1 [1]
Component Drugs Pyrazinamide   DM4IF32 Celecoxib   DM6LOQU
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 Celecoxib
Disease Entry ICD 11 Status REF
Dysmenorrhea GA34.3 Approved [4]
Lung cancer 2C25.0 Approved [4]
Osteoarthritis FA00-FA05 Approved [4]
Rheumatoid arthritis FA20 Approved [5]
Pain MG30-MG3Z Phase 3 [5]
Colon cancer 2B90.Z Investigative [4]
Familial adenomatous polyposis 2B90.Y Investigative [4]
Precancerous condition N.A. Investigative [4]
Celecoxib Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Prostaglandin G/H synthase 2 (COX-2) TTVKILB PGH2_HUMAN Inhibitor [11]
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Celecoxib Interacts with 5 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [12]
Sulfotransferase 1A1 (SULT1A1) DEYWLRK ST1A1_HUMAN Metabolism [13]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [14]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [15]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [16]
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References

1 ClinicalTrials.gov (NCT02602509) Evaluating Celecoxib Activity in Mycobacterium Tuberculosis: A Whole Blood Bactericidal Activity Study in Healthy Volunteers
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 Celecoxib FDA Label
5 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: 2892).
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 Pfizer. Product Development Pipeline. March 31 2009.
12 Major role of human liver microsomal cytochrome P450 2C9 (CYP2C9) in the oxidative metabolism of celecoxib, a novel cyclooxygenase-II inhibitor. J Pharmacol Exp Ther. 2000 May;293(2):453-9.
13 Sulfonation of 17beta-estradiol and inhibition of sulfotransferase activity by polychlorobiphenylols and celecoxib in channel catfish, Ictalurus punctatus. Aquat Toxicol. 2007 Mar 10;81(3):286-92.
14 Celecoxib is a substrate of CYP2D6: impact on celecoxib metabolism in individuals with CYP2C9*3 variants. Drug Metab Pharmacokinet. 2018 Oct;33(5):219-227.
15 Cytochrome P450 2C8 pharmacogenetics: a review of clinical studies. Pharmacogenomics. 2009 Sep;10(9):1489-510.
16 Drug interactions in dentistry: the importance of knowing your CYPs. J Am Dent Assoc. 2004 Mar;135(3):298-311.