Details of the Drug Combination

General Information of Drug Combination (ID: DCBMOE7)

• Drug Combination Name: Artemisinin + Cyclosporin A
• Indication: DD2; Status: Investigative [1]
• Component Drugs:
  Artemisinin (DMOY7W3): Small molecular drug
  Cyclosporin A (DMUYKBZ): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: DD2
  Zero Interaction Potency (ZIP) Score: 14.33
  Bliss Independence Score: 15.134
  Loewe Additivity Score: 11.251
  LHighest Single Agent (HSA) Score: 10.644

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Artemisinin

Disease Entry	ICD 11	Status	REF
Malaria	1F40-1F45	Approved	[2]

Artemisinin Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Plasmodium Dihydroorotate dehydrogenase (Malaria DHOdehase)	TT3PQ2Y	PYRD_PLAF7	Inhibitor	[2]
Sarcoplasmic/endoplasmic reticulum calcium ATPase (ATP2A)	TTZVSJ2	NOUNIPROTAC	Inhibitor	[2]

Artemisinin Interacts with 4 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[13]
Cytochrome P450 2A6 (CYP2A6)	DEJVYAZ	CP2A6_HUMAN	Metabolism	[14]
Glutathione S-transferase alpha-1 (GSTA1)	DE4ZHS1	GSTA1_HUMAN	Metabolism	[15]
Cytochrome P450 2B6 (CYP2B6)	DEPKLMQ	CP2B6_HUMAN	Metabolism	[13]

Artemisinin Interacts with 10 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Glutathione S-transferase A1 (GSTA1)	OTA7K5XA	GSTA1_HUMAN	Decreases Activity	[15]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Expression	[16]
Cytochrome P450 2B6 (CYP2B6)	OTOYO4S7	CP2B6_HUMAN	Increases Expression	[16]
Cytochrome P450 1A2 (CYP1A2)	OTLLBX48	CP1A2_HUMAN	Decreases Activity	[17]
Cytochrome P450 2C19 (CYP2C19)	OTFMJYYE	CP2CJ_HUMAN	Decreases Activity	[17]
Glutathione S-transferase P (GSTP1)	OTLP0A0Y	GSTP1_HUMAN	Decreases Activity	[15]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Expression	[16]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Activity	[18]
Isocitrate dehydrogenase subunit alpha, mitochondrial (IDH3A)	OT5QQB5L	IDH3A_HUMAN	Decreases Expression	[18]
Nuclear receptor subfamily 1 group I member 3 (NR1I3)	OTS3SGH7	NR1I3_HUMAN	Increases Activity	[19]

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

• [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] 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] Antimalarial artemisinin drugs induce cytochrome P450 and MDR1 expression by activation of xenosensors pregnane X receptor and constitutive androstane receptor. Mol Pharmacol. 2005 Jun;67(6):1954-65.
• [14] Identification of the human cytochrome P450 enzymes involved in the in vitro metabolism of artemisinin. Br J Clin Pharmacol. 1999 Oct;48(4):528-35.
• [15] Inhibition of glutathione S-transferases by antimalarial drugs possible implications for circumventing anticancer drug resistance. Int J Cancer. 2002 Feb 10;97(5):700-5.
• [16] Antimalarial artemisinin drugs induce cytochrome P450 and MDR1 expression by activation of xenosensors pregnane X receptor and constitutive androstane receptor. Mol Pharmacol. 2005 Jun;67(6):1954-65.
• [17] 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.
• [18] Identification of Compounds That Inhibit Estrogen-Related Receptor Alpha Signaling Using High-Throughput Screening Assays. Molecules. 2019 Feb 27;24(5):841. doi: 10.3390/molecules24050841.
• [19] In vivo and mechanistic evidence of nuclear receptor CAR induction by artemisinin. Eur J Clin Invest. 2006 Sep;36(9):647-53. doi: 10.1111/j.1365-2362.2006.01700.x.