Details of the Drug Combination

General Information of Drug Combination (ID: DCFMJTL)

• Drug Combination Name: Tiagabine + NARINGENIN
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Tiagabine (DMKSQG0): Small molecular drug
  NARINGENIN (DMHAZLM): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 11.37
  Bliss Independence Score: 11.37
  Loewe Additivity Score: 13.56
  LHighest Single Agent (HSA) Score: 13.58

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Tiagabine

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

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	[3]
GABA transporter GAT-1 (SLC6A1)	TTPRKM0	SC6A1_HUMAN	Inhibitor	[4]

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	[5]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[6]

NARINGENIN Interacts with 5 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Aromatase (CYP19A1)	TTSZLWK	CP19A_HUMAN	Inhibitor	[7]
Estradiol 17 beta-dehydrogenase 1 (17-beta-HSD1)	TTIWB6L	DHB1_HUMAN	Inhibitor	[8]
Estrogen receptor beta (ESR2)	TTOM3J0	ESR2_HUMAN	Inhibitor	[9]
Lactoylglutathione lyase (GLO1)	TTV9A7R	LGUL_HUMAN	Inhibitor	[10]
Cytochrome P450 1B1 (CYP1B1)	TTI84H7	CP1B1_HUMAN	Inhibitor	[11]

NARINGENIN Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[12]

NARINGENIN Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 105D7 (cyp105)	DECV2ME	CYP28_STRAW	Metabolism	[13]

References

• [1] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
• [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: 4818).
• [3] Glutamate- and GABA-based CNS therapeutics. Curr Opin Pharmacol. 2006 Feb;6(1):7-17.
• [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. (Target id: 929).
• [5] Enzyme induction and inhibition by new antiepileptic drugs: a review of human studies. Fundam Clin Pharmacol. 2000 Jul-Aug;14(4):301-19.
• [6] Actual and Predicted Pharmacokinetic Interactions Between Anticonvulsants and Antiretrovirals.
• [7] Pharmacophore modeling strategies for the development of novel nonsteroidal inhibitors of human aromatase (CYP19). Bioorg Med Chem Lett. 2010 May 15;20(10):3050-64.
• [8] Discovery of nonsteroidal 17beta-hydroxysteroid dehydrogenase 1 inhibitors by pharmacophore-based screening of virtual compound libraries. J Med Chem. 2008 Jul 24;51(14):4188-99.
• [9] Subtle side-chain modifications of the hop phytoestrogen 8-prenylnaringenin result in distinct agonist/antagonist activity profiles for estrogen re... J Med Chem. 2006 Dec 14;49(25):7357-65.
• [10] Structure-activity relationship of human GLO I inhibitory natural flavonoids and their growth inhibitory effects. Bioorg Med Chem. 2008 Apr 1;16(7):3969-75.
• [11] Selective inhibition of methoxyflavonoids on human CYP1B1 activity. Bioorg Med Chem. 2010 Sep 1;18(17):6310-5.
• [12] Flavonoid permeability across an in situ model of the blood-brain barrier. Free Radic Biol Med. 2004 Mar 1;36(5):592-604.
• [13] The metagenome of Caracolus marginella gut microbiome using culture independent approaches and shotgun sequencing. Data Brief. 2017 Nov 22;16:501-505.