Details of the Drug Combination

General Information of Drug Combination (ID: DCPMXOU)

• Drug Combination Name: Amantadine + Tiagabine
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Amantadine (DMS3YE9): Small molecular drug
  Tiagabine (DMKSQG0): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 12.9
  Bliss Independence Score: 12.9
  Loewe Additivity Score: 15.52
  LHighest Single Agent (HSA) Score: 15.55

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 Tiagabine

Disease Entry	ICD 11	Status	REF
Epilepsy	8A60-8A68	Approved	[4]
Anxiety disorder	6B00-6B0Z	Phase 2	[4]

Tiagabine Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Gamma-aminobutyric acid uptake (GABAU)	TTV9MQG	NOUNIPROTAC	Inhibitor	[11]
GABA transporter GAT-1 (SLC6A1)	TTPRKM0	SC6A1_HUMAN	Inhibitor	[12]

Tiagabine Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[13]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[14]

Tiagabine Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Aromatase (CYP19A1)	OTZ6XF74	CP19A_HUMAN	Decreases Activity	[15]
Sodium- and chloride-dependent GABA transporter 1 (SLC6A1)	OTLCJJF3	SC6A1_HUMAN	Decreases Activity	[16]

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] 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: 4818).
• [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] Glutamate- and GABA-based CNS therapeutics. Curr Opin Pharmacol. 2006 Feb;6(1):7-17.
• [12] 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. (Target id: 929).
• [13] Enzyme induction and inhibition by new antiepileptic drugs: a review of human studies. Fundam Clin Pharmacol. 2000 Jul-Aug;14(4):301-19.
• [14] Actual and Predicted Pharmacokinetic Interactions Between Anticonvulsants and Antiretrovirals.
• [15] Inhibition of human aromatase complex (CYP19) by antiepileptic drugs. Toxicol In Vitro. 2008 Feb;22(1):146-53.
• [16] GABA transporter deficiency causes tremor, ataxia, nervousness, and increased GABA-induced tonic conductance in cerebellum. J Neurosci. 2005 Mar 23;25(12):3234-45. doi: 10.1523/JNEUROSCI.3364-04.2005.