Details of the Drug Combination

General Information of Drug Combination (ID: DCN19JN)

Drug Combination Name
Pyrazinamide Pargyline
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Pyrazinamide   DM4IF32 Pargyline   DMM0HR1
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: KBM-7
Zero Interaction Potency (ZIP) Score: 29.14
Bliss Independence Score: 29.14
Loewe Additivity Score: 43.52
LHighest Single Agent (HSA) Score: 43.54

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 Pargyline
Disease Entry ICD 11 Status REF
Hypertension BA00-BA04 Approved [4]
Muscular dystrophy 8C70 Patented [5]
Skin imperfections EK71 Patented [5]
Pargyline Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Monoamine oxidase (MAO) TT32XQJ NOUNIPROTAC Inhibitor [5]
Monoamine oxidase type B (MAO-B) TTGP7BY AOFB_HUMAN Inhibitor [11]
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Pargyline Interacts with 2 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 2B6 (CYP2B6) OTOYO4S7 CP2B6_HUMAN Decreases Activity [12]
Amine oxidase B (MAOB) OTTDFM1O AOFB_HUMAN Decreases Activity [13]
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References

1 Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
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. 2015
5 Novel monoamine oxidase inhibitors: a patent review (2012 - 2014).Expert Opin Ther Pat. 2015 Jan;25(1):91-110.
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 Dose-dependent activation of distinct hypertrophic pathways by serotonin in cardiac cells. Am J Physiol Heart Circ Physiol. 2009 Aug;297(2):H821-8.
12 Evaluation of metabolism dependent inhibition of CYP2B6 mediated bupropion hydroxylation in human liver microsomes by monoamine oxidase inhibitors and prediction of potential as perpetrators of drug interaction. Chem Biol Interact. 2015 Mar 25;230:9-20.
13 Combining initro and in silico approaches to evaluate the multifunctional profile of rosmarinic acid from Blechnum brasiliense on targets related to neurodegeneration. Chem Biol Interact. 2016 Jul 25;254:135-45.