Details of the Drug Combination

General Information of Drug Combination (ID: DC7GFNG)

• Drug Combination Name: Artemisinin + Sulfapyridine
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Artemisinin (DMOY7W3): Small molecular drug
  Sulfapyridine (DMIUYFH): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 25.87
  Bliss Independence Score: 25.87
  Loewe Additivity Score: 34.46
  LHighest Single Agent (HSA) Score: 34.51

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	[4]
Cytochrome P450 2A6 (CYP2A6)	DEJVYAZ	CP2A6_HUMAN	Metabolism	[5]
Glutathione S-transferase alpha-1 (GSTA1)	DE4ZHS1	GSTA1_HUMAN	Metabolism	[6]
Cytochrome P450 2B6 (CYP2B6)	DEPKLMQ	CP2B6_HUMAN	Metabolism	[4]

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	[6]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Expression	[7]
Cytochrome P450 2B6 (CYP2B6)	OTOYO4S7	CP2B6_HUMAN	Increases Expression	[7]
Cytochrome P450 1A2 (CYP1A2)	OTLLBX48	CP1A2_HUMAN	Decreases Activity	[8]
Cytochrome P450 2C19 (CYP2C19)	OTFMJYYE	CP2CJ_HUMAN	Decreases Activity	[8]
Glutathione S-transferase P (GSTP1)	OTLP0A0Y	GSTP1_HUMAN	Decreases Activity	[6]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Expression	[7]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Activity	[9]
Isocitrate dehydrogenase subunit alpha, mitochondrial (IDH3A)	OT5QQB5L	IDH3A_HUMAN	Decreases Expression	[9]
Nuclear receptor subfamily 1 group I member 3 (NR1I3)	OTS3SGH7	NR1I3_HUMAN	Increases Activity	[10]

Indication(s) of Sulfapyridine

Disease Entry	ICD 11	Status	REF
Dermatitis herpetiformis	EB44	Approved	[3]

Sulfapyridine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Bacterial Dihydropteroate synthetase (Bact folP)	TT4ILYC	DHPS_ECOLI	Inhibitor	[11]

Sulfapyridine Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
RNA cytidine acetyltransferase (hALP)	DEZV4AP	NAT10_HUMAN	Metabolism	[12]

Sulfapyridine Interacts with 6 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Growth-regulated alpha protein (CXCL1)	OT3WCTZV	GROA_HUMAN	Decreases Secretion	[13]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Decreases Secretion	[13]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Decreases Secretion	[13]
Metalloproteinase inhibitor 2 (TIMP2)	OT8S1RRP	TIMP2_HUMAN	Increases Expression	[14]
Arylamine N-acetyltransferase 2 (NAT2)	OTBPDQOY	ARY2_HUMAN	Increases Acetylation	[15]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2)	OTW8V2V1	ABCG2_HUMAN	Increases Transport	[15]

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] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [4] 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.
• [5] 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.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] A confirmatory method for the simultaneous extraction, separation, identification and quantification of Tetracycline, Sulphonamide, Trimethoprim an... J Chromatogr A. 2009 Nov 13;1216(46):8110-6.
• [12] Effects of NAT2 polymorphism on SASP pharmacokinetics in Chinese population. Clin Chim Acta. 2009 Sep;407(1-2):30-5.
• [13] The effect of sulfasalazine on rheumatoid arthritic synovial tissue chemokine production. Exp Mol Pathol. 2002 Oct;73(2):84-92. doi: 10.1006/exmp.2002.2460.
• [14] Effects of sulfasalazine and its metabolites on steady state messenger RNA concentrations for inflammatory cytokines, matrix metalloproteinases, and tissue inhibitors of metalloproteinase in rheumatoid synovial fibroblasts. J Rheumatol. 2000 Mar;27(3):653-60.
• [15] Pharmacogenetic characterization of sulfasalazine disposition based on NAT2 and ABCG2 (BCRP) gene polymorphisms in humans. Clin Pharmacol Ther. 2008 Jul;84(1):95-103.