Details of the Drug Combination

General Information of Drug Combination (ID: DCP4CIA)

Drug Combination Name
T-3.5 Atovaquone
Indication
Disease Entry Status REF
DD2 Investigative [1]
Component Drugs T-3.5   DM3Q1HL Atovaquone   DMY4UMW
N.A. Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: DD2
Zero Interaction Potency (ZIP) Score: 1.65
Bliss Independence Score: 3.542
Loewe Additivity Score: 2.046
LHighest Single Agent (HSA) Score: 1.369

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of T-3.5
Disease Entry ICD 11 Status REF
Malaria 1F40-1F45 Investigative [2]
Indication(s) of Atovaquone
Disease Entry ICD 11 Status REF
Fungal infection 1F29-1F2F Approved [3]
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]
------------------------------------------------------------------------------------
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]
------------------------------------------------------------------------------------
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]
------------------------------------------------------------------------------------

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 ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
3 The fight against drug-resistant malaria: novel plasmodial targets and antimalarial drugs. Curr Med Chem. 2008;15(2):161-71.
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.