Details of the Drug Combination

General Information of Drug Combination (ID: DC223XE)

Drug Combination Name
BREQUINAR Atovaquone
Indication
Disease Entry Status REF
Hepatoblastoma Investigative [1]
Component Drugs BREQUINAR   DMKGM42 Atovaquone   DMY4UMW
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: HB3
Zero Interaction Potency (ZIP) Score: 14.013
Bliss Independence Score: 17.906
Loewe Additivity Score: 6.714
LHighest Single Agent (HSA) Score: 6.782

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of BREQUINAR
Disease Entry ICD 11 Status REF
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 2 [2]
Acute myeloid leukaemia 2A60 Phase 1/2 [3]
BREQUINAR Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Dihydroorotate dehydrogenase (DHODH) TTLVP78 PYRD_HUMAN Modulator [5]
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Indication(s) of Atovaquone
Disease Entry ICD 11 Status REF
Fungal infection 1F29-1F2F Approved [4]
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 [6]
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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 [7]
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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 [8]
Cytochrome P450 1A2 (CYP1A2) OTLLBX48 CP1A2_HUMAN Increases Activity [9]
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References

1 Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy.Hum Genet. 2018 Apr;137(4):293-303. doi: 10.1007/s00439-018-1882-3. Epub 2018 Apr 24.
2 ClinicalTrials.gov (NCT04575038) CRISIS2: A Phase 2 Study of the Safety and Antiviral Activity of Brequinar in Non-hospitalized Pts With COVID-19 (CRISIS2). U.S. National Institutes of Health.
3 ClinicalTrials.gov (NCT03760666) A Study of Brequinar in Subjects With Relapsed/Refractory Acute Myeloid Leukemia. U.S. National Institutes of Health.
4 The fight against drug-resistant malaria: novel plasmodial targets and antimalarial drugs. Curr Med Chem. 2008;15(2):161-71.
5 DOI: 10.1203/00006450-198807000-00137
6 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.
7 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.
8 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.
9 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.