Details of the Drug Combination

General Information of Drug Combination (ID: DCME91O)

• Drug Combination Name: Atovaquone + Cyclosporin A
• Indication: DD2; Status: Investigative [1]
• Component Drugs:
  Atovaquone (DMY4UMW): Small molecular drug
  Cyclosporin A (DMUYKBZ): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: DD2
  Zero Interaction Potency (ZIP) Score: 6.396
  Bliss Independence Score: 5.008
  Loewe Additivity Score: 0.208
  LHighest Single Agent (HSA) Score: 4.25

Molecular Interaction Atlas of This Drug Combination

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	[13]

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	[14]

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	[15]
Cytochrome P450 1A2 (CYP1A2)	OTLLBX48	CP1A2_HUMAN	Increases Activity	[16]

Indication(s) of Cyclosporin A

Disease Entry	ICD 11	Status	REF
Adult acute monocytic leukemia	N.A.	Approved	[3]
Bronchiolitis obliterans syndrome	N.A.	Approved	[4]
Large granular lymphocytic leukemia	2A90.1	Approved	[5]
Leukemia	N.A.	Approved	[6]
Lupus nephritis	4A40.0Y	Approved	[7]
Myeloid leukaemia	2B33.1	Approved	[8]
Psoriasis	EA90	Approved	[9]
Xerophthalmia	5B55.Y	Approved	[10]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 1	[11]
Corneal disease	9A78.Z	Investigative	[12]

References

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• [2] The fight against drug-resistant malaria: novel plasmodial targets and antimalarial drugs. Curr Med Chem. 2008;15(2):161-71.
• [3] Clinical and biological impact of ATP-binding cassette transporter activity in adult acute myeloid leukemia. Haematologica. 2023 Jan 1;108(1):61-68.
• [4] Bronchiolitis obliterans syndrome is associated with increased senescent lymphocytes in the small airways. J Heart Lung Transplant. 2021 Feb;40(2):108-119.
• [5] Rituximab for rheumatoid arthritis-associated large granular lymphocytic leukemia, a retrospective case series. Semin Arthritis Rheum. 2020 Oct;50(5):1109-1113.
• [6] Cyclosporin A protects JEG-3 cells against oxidative stress-induced apoptosis by inhibiting the p53 and JNK/p38 signaling pathways. Reprod Biol Endocrinol. 2020 Oct 12;18(1):100.
• [7] Efficacy and safety of Iguratimod as an add-on therapy for refractory lupus nephritis: A preliminary investigational study. Front Immunol. 2023 Mar 8;14:1062919.
• [8] Efficacy and safety of extended duration letermovir prophylaxis in recipients of haematopoietic stem-cell transplantation at risk of cytomegalovirus infection: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Haematol. 2024 Feb;11(2):e127-e135.
• [9] Pustular psoriasis. Cutis. 1993 Jan;51(1):29-32.
• [10] Cyclosporin A (CyA) in primary Sj?gren's syndrome: a double blind study. Ann Rheum Dis. 1986 Sep;45(9):732-5.
• [11] Why Choose Cyclosporin A as First-line Therapy in COVID-19 Pneumonia. Reumatol Clin. 2020 Apr 16;S1699-258X(20)30044-9.
• [12] Anti-inflammatory therapy of dry eye. Ocul Surf. 2003 Jan;1(1):31-6.
• [13] 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.
• [14] 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.
• [15] 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.
• [16] 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.