Details of the Drug Combination

General Information of Drug Combination (ID: DCIJ5KI)

• Drug Combination Name: Lefaxin + Tiagabine
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Lefaxin (DM0CEY3): Small molecular drug
  Tiagabine (DMKSQG0): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 1.41
  Bliss Independence Score: 1.41
  Loewe Additivity Score: 3.86
  LHighest Single Agent (HSA) Score: 3.87

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Lefaxin

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[2]

Lefaxin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Coagulation factor Xa (F10)	TTCIHJA	FA10_HUMAN	Inhibitor	[2]

Lefaxin Interacts with 11 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Acetylcholinesterase (ACHE)	OT2H8HG6	ACES_HUMAN	Decreases Activity	[4]
Superoxide dismutase (SOD1)	OT39TA1L	SODC_HUMAN	Affects Expression	[5]
Catalase (CAT)	OTHEBX9R	CATA_HUMAN	Decreases Expression	[5]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Decreases Expression	[5]
Glutathione peroxidase 1 (GPX1)	OTE2O72Q	GPX1_HUMAN	Decreases Expression	[5]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[5]
DNA cytosine-5)-methyltransferase 1 (DNMT1)	OTM2DGTK	DNMT1_HUMAN	Decreases Expression	[5]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Decreases Expression	[5]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Decreases Expression	[5]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Decreases Expression	[5]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Affects Binding	[6]

Indication(s) of Tiagabine

Disease Entry	ICD 11	Status	REF
Epilepsy	8A60-8A68	Approved	[3]
Anxiety disorder	6B00-6B0Z	Phase 2	[3]

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	[7]
GABA transporter GAT-1 (SLC6A1)	TTPRKM0	SC6A1_HUMAN	Inhibitor	[8]

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	[9]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[10]

Tiagabine Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Aromatase (CYP19A1)	OTZ6XF74	CP19A_HUMAN	Decreases Activity	[11]
Sodium- and chloride-dependent GABA transporter 1 (SLC6A1)	OTLCJJF3	SC6A1_HUMAN	Decreases Activity	[12]

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] Novel approaches to the treatment of thrombosis. Trends Pharmacol Sci. 2002 Jan;23(1):25-32.
• [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: 4818).
• [4] In vitro kinetic interactions of DEET, pyridostigmine and organophosphorus pesticides with human cholinesterases. Chem Biol Interact. 2011 Apr 25;190(2-3):79-83.
• [5] The Val16Ala-SOD2 polymorphism affects cyto-genotoxicity of pyridostigmine bromide on human peripheral blood mononuclear cells. Toxicol In Vitro. 2019 Oct;60:237-244.
• [6] Binding of pyridostigmine bromide, N,N-diethyl-m-toluamide and permethrin, alone and in combinations, to human serum albumin. Arch Toxicol. 2002 May;76(4):203-8. doi: 10.1007/s00204-002-0328-8. Epub 2002 Mar 9.
• [7] Glutamate- and GABA-based CNS therapeutics. Curr Opin Pharmacol. 2006 Feb;6(1):7-17.
• [8] 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).
• [9] Enzyme induction and inhibition by new antiepileptic drugs: a review of human studies. Fundam Clin Pharmacol. 2000 Jul-Aug;14(4):301-19.
• [10] Actual and Predicted Pharmacokinetic Interactions Between Anticonvulsants and Antiretrovirals.
• [11] Inhibition of human aromatase complex (CYP19) by antiepileptic drugs. Toxicol In Vitro. 2008 Feb;22(1):146-53.
• [12] 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.