Details of the Drug Combination

General Information of Drug Combination (ID: DCVZCQY)

• Drug Combination Name: Amantadine + Fomepizole
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Amantadine (DMS3YE9): Small molecular drug
  Fomepizole (DM6VOWQ): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 1.78
  Bliss Independence Score: 1.78
  Loewe Additivity Score: 3.92
  LHighest Single Agent (HSA) Score: 3.97

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Amantadine

Disease Entry	ICD 11	Status	REF
Influenza A virus infection	1E30	Approved	[2]
Parkinsonian disorder	N.A.	Approved	[3]
Postencephalitic Parkinson disease	N.A.	Approved	[3]

Amantadine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Influenza M2 protein (Influ M)	TTXT3PU	M2_I34A1	Inhibitor	[5]

Amantadine Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Organic cation transporter 2 (SLC22A2)	DT9IDPW	S22A2_HUMAN	Substrate	[6]

Amantadine Interacts with 8 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Interferon alpha-inducible protein 6 (IFI6)	OTWOOAM4	IFI6_HUMAN	Increases Expression	[7]
Microtubule-associated protein 2 (MAP2)	OT6UYT3X	MTAP2_HUMAN	Decreases Expression	[8]
Interferon alpha/beta receptor 1 (IFNAR1)	OTD4OOFK	INAR1_HUMAN	Affects Expression	[7]
Tyrosine-protein kinase JAK1 (JAK1)	OT0X3D17	JAK1_HUMAN	Increases Expression	[7]
2'-5'-oligoadenylate synthase 2 (OAS2)	OT64CCTM	OAS2_HUMAN	Increases Expression	[7]
Interferon alpha-inducible protein 27, mitochondrial (IFI27)	OTI2XGIT	IFI27_HUMAN	Increases Expression	[7]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Decreases Activity	[9]
Tyrosyl-DNA phosphodiesterase 1 (TDP1)	OTYINMBR	TYDP1_HUMAN	Decreases Activity	[10]

Indication(s) of Fomepizole

Disease Entry	ICD 11	Status	REF
Athylene glycol or methanol poisoning	NE61	Approved	[4]

Fomepizole Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Alcohol dehydrogenase 1A (ADH1A)	TT5AHZ0	ADH1A_HUMAN	Modulator	[11]

Fomepizole Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2E1 (CYP2E1)	DEVDYN7	CP2E1_HUMAN	Metabolism	[12]

Fomepizole Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2E1 (CYP2E1)	OTHQ17JG	CP2E1_HUMAN	Decreases Activity	[13]

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] 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: 4128).
• [3] Amantadine FDA Label
• [4] Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
• [5] Discovery of spiro-piperidine inhibitors and their modulation of the dynamics of the M2 proton channel from influenza A virus. J Am Chem Soc. 2009 Jun 17;131(23):8066-76.
• [6] Human neurons express the polyspecific cation transporter hOCT2, which translocates monoamine neurotransmitters, amantadine, and memantine. Mol Pharmacol. 1998 Aug;54(2):342-52.
• [7] Interferon signal transduction of biphenyl dimethyl dicarboxylate/amantadine and anti-HBV activity in HepG2 2.2.15. Arch Pharm Res. 2006 May;29(5):405-11. doi: 10.1007/BF02968591.
• [8] Establishment of a 13 genes-based molecular prediction score model to discriminate the neurotoxic potential of food relevant-chemicals. Toxicol Lett. 2022 Feb 1;355:1-18. doi: 10.1016/j.toxlet.2021.10.013. Epub 2021 Nov 5.
• [9] Identification of human Ether--go-go related gene modulators by three screening platforms in an academic drug-discovery setting. Assay Drug Dev Technol. 2010 Dec;8(6):727-42. doi: 10.1089/adt.2010.0331.
• [10] Aminoadamantanes containing monoterpene-derived fragments as potent tyrosyl-DNA phosphodiesterase 1 inhibitors. Bioorg Chem. 2018 Feb;76:392-399. doi: 10.1016/j.bioorg.2017.12.005. Epub 2017 Dec 9.
• [11] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [12] Treatment of patients with ethylene glycol or methanol poisoning: focus on fomepizole. Open Access Emerg Med. 2010 Aug 24;2:67-75.
• [13] Chemical inhibitors of cytochrome P450 isoforms in human liver microsomes: a re-evaluation of P450 isoform selectivity. Eur J Drug Metab Pharmacokinet. 2011 Mar;36(1):1-16.