Details of the Drug Combination

General Information of Drug Combination (ID: DC5XJWK)

Drug Combination Name

Artemisinin Lacidipine

Indication

Disease Entry	Status	REF
DD2	Investigative	[1]

Component Drugs

Artemisinin DMOY7W3

Lacidipine DMQP5I3

Small molecular drug

N.A.

2D MOL

3D MOL

High-throughput Screening Result

Testing Cell Line: DD2

Zero Interaction Potency (ZIP) Score: 13.532

Bliss Independence Score: 9.187

Loewe Additivity Score: 14.329

LHighest Single Agent (HSA) Score: 14.25

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)

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]
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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	[3]
Cytochrome P450 2A6 (CYP2A6)	DEJVYAZ	CP2A6_HUMAN	Metabolism	[4]
Glutathione S-transferase alpha-1 (GSTA1)	DE4ZHS1	GSTA1_HUMAN	Metabolism	[5]
Cytochrome P450 2B6 (CYP2B6)	DEPKLMQ	CP2B6_HUMAN	Metabolism	[3]
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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	[5]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Expression	[6]
Cytochrome P450 2B6 (CYP2B6)	OTOYO4S7	CP2B6_HUMAN	Increases Expression	[6]
Cytochrome P450 1A2 (CYP1A2)	OTLLBX48	CP1A2_HUMAN	Decreases Activity	[7]
Cytochrome P450 2C19 (CYP2C19)	OTFMJYYE	CP2CJ_HUMAN	Decreases Activity	[7]
Glutathione S-transferase P (GSTP1)	OTLP0A0Y	GSTP1_HUMAN	Decreases Activity	[5]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Expression	[6]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Activity	[8]
Isocitrate dehydrogenase subunit alpha, mitochondrial (IDH3A)	OT5QQB5L	IDH3A_HUMAN	Decreases Expression	[8]
Nuclear receptor subfamily 1 group I member 3 (NR1I3)	OTS3SGH7	NR1I3_HUMAN	Increases Activity	[9]
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⏷ Show the Full List of 10 DOT(s)

Lacidipine Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[11]
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Lacidipine Interacts with 5 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Estrogen receptor (ESR1)	OTKLU61J	ESR1_HUMAN	Increases Activity	[10]
Androgen receptor (AR)	OTUBKAZZ	ANDR_HUMAN	Increases Activity	[10]
Peroxisome proliferator-activated receptor gamma (PPARG)	OTHMARHO	PPARG_HUMAN	Increases Activity	[10]
Peroxisome proliferator-activated receptor delta (PPARD)	OTI4WTOP	PPARD_HUMAN	Increases Activity	[10]
Bile acid receptor (NR1H4)	OTWZLPTB	NR1H4_HUMAN	Increases Activity	[10]
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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	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.
4	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.
5	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.
6	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.
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.
8	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.
9	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.
10	Quantitative high-throughput profiling of environmental chemicals and drugs that modulate farnesoid X receptor. Sci Rep. 2014 Sep 26;4:6437. doi: 10.1038/srep06437.
11	The effects of lacidipine on the steady/state plasma concentrations of simvastatin in healthy subjects. Br J Clin Pharmacol. 2001 Feb;51(2):147-52.