Details of the Drug Combination

General Information of Drug Combination (ID: DC4REMZ)

Drug Combination Name

Levamisole Dronedarone

Indication

Disease Entry	Status	REF
Chronic myelogenous leukemia	Investigative	[1]

Component Drugs

Levamisole DM5EN79

Dronedarone DMA8FS5

Small molecular drug

2D MOL

3D MOL

High-throughput Screening Result

Testing Cell Line: KBM-7

Zero Interaction Potency (ZIP) Score: 67.39

Bliss Independence Score: 67.39

Loewe Additivity Score: 81.73

LHighest Single Agent (HSA) Score: 81.73

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)

Indication(s) of Levamisole

Disease Entry	ICD 11	Status	REF
Parasitic infection	1D0Y-1G2Z	Approved	[2]
Colon cancer	2B90.Z	Withdrawn from market	[3]

Levamisole Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Alkaline phosphatase tissue-nonspecific (ALPL)	TTMR5UV	PPBT_HUMAN	Inhibitor	[5]
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Levamisole Interacts with 8 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Decreases Expression	[6]
Endothelin-1 (EDN1)	OTZCACEG	EDN1_HUMAN	Decreases Expression	[6]
Retinoblastoma-associated protein (RB1)	OTQJUJMZ	RB_HUMAN	Decreases Expression	[6]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[6]
Clusterin (CLU)	OTQGG0JM	CLUS_HUMAN	Decreases Expression	[6]
Nitric oxide synthase 3 (NOS3)	OTLDT7NR	NOS3_HUMAN	Decreases Expression	[6]
Bcl-2 homologous antagonist/killer (BAK1)	OTDP6ILW	BAK_HUMAN	Increases Expression	[6]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Decreases Expression	[7]
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⏷ Show the Full List of 8 DOT(s)

Indication(s) of Dronedarone

Disease Entry	ICD 11	Status	REF
Angina pectoris	BA40	Approved	[4]
Atrial fibrillation	BC81.3	Withdrawn from market	[4]

Dronedarone Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Voltage-gated potassium channel Kv1.5 (KCNA5)	TTW0CMT	KCNA5_HUMAN	Blocker	[8]
Potassium channel unspecific (KC)	TT1VOHK	NOUNIPROTAC	Inhibitor	[9]
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Dronedarone Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[10]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[11]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[12]
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Dronedarone Interacts with 21 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Decreases Response To Substance	[13]
Cytochrome P450 2D6 (CYP2D6)	OTZJC802	CP2D6_HUMAN	Decreases Response To Substance	[13]
Cytochrome P450 3A5 (CYP3A5)	OTSXFBXB	CP3A5_HUMAN	Decreases Response To Substance	[13]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Increases Expression	[14]
DNA topoisomerase 2-alpha (TOP2A)	OT6LPS08	TOP2A_HUMAN	Decreases Expression	[13]
Cyclin-dependent kinase 4 (CDK4)	OT7EP05T	CDK4_HUMAN	Decreases Expression	[13]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Phosphorylation	[13]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Decreases Expression	[13]
Cyclin-dependent kinase 2 (CDK2)	OTB5DYYZ	CDK2_HUMAN	Decreases Expression	[13]
G1/S-specific cyclin-D3 (CCND3)	OTNKPQ22	CCND3_HUMAN	Decreases Expression	[13]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[14]
Caspase-7 (CASP7)	OTAPJ040	CASP7_HUMAN	Increases Activity	[14]
Cyclin-dependent kinase 6 (CDK6)	OTR95N0X	CDK6_HUMAN	Decreases Expression	[13]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Decreases Activity	[15]
Cytochrome P450 1B1 (CYP1B1)	OTYXFLSD	CP1B1_HUMAN	Decreases Activity	[16]
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Increases Metabolism	[13]
Cytochrome P450 2C19 (CYP2C19)	OTFMJYYE	CP2CJ_HUMAN	Increases Metabolism	[13]
Cytochrome P450 2E1 (CYP2E1)	OTHQ17JG	CP2E1_HUMAN	Increases Metabolism	[13]
Cytochrome P450 2B6 (CYP2B6)	OTOYO4S7	CP2B6_HUMAN	Increases Metabolism	[13]
Cytochrome P450 3A7 (CYP3A7)	OTTCDHHM	CP3A7_HUMAN	Increases Metabolism	[13]
Cytochrome P450 2C18 (CYP2C18)	OTY687L9	CP2CI_HUMAN	Increases Metabolism	[13]
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⏷ Show the Full List of 21 DOT(s)

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	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
3	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7210).
4	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7465).
5	Characterization of rat heart alkaline phosphatase isoenzymes and modulation of activity. Braz J Med Biol Res. 2008 Jul;41(7):600-9.
6	Levamisole induced apoptosis in cultured vascular endothelial cells. Br J Pharmacol. 2000 Dec;131(8):1577-83.
7	Levamisole can reduce the high serum tumour necrosis factor-alpha level to a normal level in patients with erosive oral lichen planus. Clin Exp Dermatol. 2007 May;32(3):308-10. doi: 10.1111/j.1365-2230.2006.02343.x.
8	New antiarrhythmic agents for atrial fibrillation and atrial flutter. Expert Opin Emerg Drugs. 2005 May;10(2):311-22.
9	Antibodies and venom peptides: new modalities for ion channels. Nat Rev Drug Discov. 2019 May;18(5):339-357.
10	Drug safety evaluation of dronedarone in atrial fibrillation. Expert Opin Drug Saf. 2012 Nov;11(6):1023-45.
11	Effect of dronedarone on the pharmacokinetics of carvedilol following oral administration to rats. Eur J Pharm Sci. 2018 Jan 1;111:13-19.
12	Inactivation of human cytochrome P450 3A4 and 3A5 by dronedarone and N-desbutyl dronedarone. Mol Pharmacol. 2016 Jan;89(1):1-13.
13	The role of hepatic cytochrome P450s in the cytotoxicity of dronedarone. Arch Toxicol. 2018 Jun;92(6):1969-1981. doi: 10.1007/s00204-018-2196-x. Epub 2018 Apr 3.
14	Mechanisms of hepatocellular toxicity associated with dronedarone--a comparison to amiodarone. Toxicol Sci. 2013 Feb;131(2):480-90. doi: 10.1093/toxsci/kfs298. Epub 2012 Nov 7.
15	Five novel single nucleotide polymorphisms in the CYP2C8 gene, one of which induces a frame-shift. Drug Metab Pharmacokinet. 2002;17(4):374-7. doi: 10.2133/dmpk.17.374.
16	Association of CYP1A1 and CYP1B1 inhibition in in vitro assays with drug-induced liver injury. J Toxicol Sci. 2021;46(4):167-176. doi: 10.2131/jts.46.167.