General Information of Drug Combination (ID: DCQTIMD)

Drug Combination Name
Atovaquone Furazolidone
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Atovaquone   DMY4UMW Furazolidone   DM3P6V7
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: 6.66
Bliss Independence Score: 6.66
Loewe Additivity Score: 20.28
LHighest Single Agent (HSA) Score: 20.28

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Atovaquone
Disease Entry ICD 11 Status REF
Fungal infection 1F29-1F2F Approved [2]
Atovaquone Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Plasmodium Dihydroorotate dehydrogenase (Malaria DHOdehase) TT3PQ2Y PYRD_PLAF7 Inhibitor [4]
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Atovaquone Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [5]
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Atovaquone Interacts with 2 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Dihydroorotate dehydrogenase (DHODH) OTAKFN78 PYRD_HUMAN Decreases Activity [6]
Cytochrome P450 1A2 (CYP1A2) OTLLBX48 CP1A2_HUMAN Increases Activity [7]
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Indication(s) of Furazolidone
Disease Entry ICD 11 Status REF
Diarrhea ME05.1 Approved [3]
Furazolidone Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Bacterial Deoxyribonucleic acid (Bact DNA) TTS1W4A NOUNIPROTAC Modulator [8]
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Furazolidone Interacts with 17 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Serine/threonine-protein kinase Chk1 (CHEK1) OTTTI622 CHK1_HUMAN Increases Expression [9]
Heme oxygenase 1 (HMOX1) OTC1W6UX HMOX1_HUMAN Increases Expression [10]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [10]
Endoplasmic reticulum chaperone BiP (HSPA5) OTFUIRAO BIP_HUMAN Increases Expression [9]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Increases Expression [11]
Growth arrest and DNA damage-inducible protein GADD45 alpha (GADD45A) OTDRV63V GA45A_HUMAN Increases Expression [12]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Increases Phosphorylation [9]
G1/S-specific cyclin-D3 (CCND3) OTNKPQ22 CCND3_HUMAN Increases Expression [11]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Phosphorylation [10]
DNA damage-inducible transcript 3 protein (DDIT3) OTI8YKKE DDIT3_HUMAN Increases Expression [9]
Breast cancer type 1 susceptibility protein (BRCA1) OT5BN6VH BRCA1_HUMAN Increases Expression [9]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [10]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [10]
Cyclin-dependent kinase 6 (CDK6) OTR95N0X CDK6_HUMAN Increases Expression [11]
Nuclear factor erythroid 2-related factor 2 (NFE2L2) OT0HENJ5 NF2L2_HUMAN Increases Expression [10]
Alkaline phosphatase, tissue-nonspecific isozyme (ALPL) OTG7J4BP PPBT_HUMAN Increases ADR [13]
Alanine aminotransferase 1 (GPT) OTOXOA0Q ALAT1_HUMAN Increases ADR [13]
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⏷ Show the Full List of 17 DOT(s)

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 The fight against drug-resistant malaria: novel plasmodial targets and antimalarial drugs. Curr Med Chem. 2008;15(2):161-71.
3 FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 011270.
4 Inhibitor binding in a class 2 dihydroorotate dehydrogenase causes variations in the membrane-associated N-terminal domain. Protein Sci. 2004 Apr;13(4):1031-42.
5 Time-dependent pharmacokinetics and drug metabolism of atovaquone plus proguanil (Malarone) when taken as chemoprophylaxis. Eur J Clin Pharmacol. 2002 Apr;58(1):19-27.
6 Kinetics of inhibition of human and rat dihydroorotate dehydrogenase by atovaquone, lawsone derivatives, brequinar sodium and polyporic acid. Chem Biol Interact. 2000 Jan 3;124(1):61-76.
7 Application of higher throughput screening (HTS) inhibition assays to evaluate the interaction of antiparasitic drugs with cytochrome P450s. Drug Metab Dispos. 2001 Jan;29(1):30-5.
8 Interaction of furazolidone with DNA. Biochim Biophys Acta. 1975 Aug 21;402(2):161-5.
9 Involvement of the activation of Nrf2/HO-1, p38 MAPK signaling pathways and endoplasmic reticulum stress in furazolidone induced cytotoxicity and S phase arrest in human hepatocyte L02 cells: modulation of curcumin. Toxicol Mech Methods. 2017 Mar;27(3):165-172. doi: 10.1080/15376516.2016.1273424. Epub 2017 Jan 8.
10 P21(Waf1/Cip1) plays a critical role in furazolidone-induced apoptosis in HepG2 cells through influencing the caspase-3 activation and ROS generation. Food Chem Toxicol. 2016 Feb;88:1-12. doi: 10.1016/j.fct.2015.12.004. Epub 2015 Dec 11.
11 Involvement of the p38 MAPK signaling pathway in S-phase cell-cycle arrest induced by Furazolidone in human hepatoma G2 cells. J Appl Toxicol. 2013 Dec;33(12):1500-5. doi: 10.1002/jat.2829. Epub 2012 Oct 30.
12 The Effect of GADD45a on Furazolidone-Induced S-Phase Cell-Cycle Arrest in Human Hepatoma G2 Cells. J Biochem Mol Toxicol. 2015 Oct;29(10):489-495. doi: 10.1002/jbt.21719. Epub 2015 Jun 11.
13 ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.