Details of the Drug Combination

General Information of Drug Combination (ID: DCIV1MQ)

Drug Combination Name
L-165041 Tiagabine
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs L-165041   DMZP7YM Tiagabine   DMKSQG0
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL is unavailable 3D MOL
High-throughput Screening Result Testing Cell Line: KBM-7
Zero Interaction Potency (ZIP) Score: 9.14
Bliss Independence Score: 9.14
Loewe Additivity Score: 11.26
LHighest Single Agent (HSA) Score: 11.27

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of L-165041
Disease Entry ICD 11 Status REF
Discovery agent N.A. Investigative [2]
L-165041 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Peroxisome proliferator-activated receptor delta (PPARD) TT2JWF6 PPARD_HUMAN Agonist [5]
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L-165041 Interacts with 5 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Fatty acid-binding protein, adipocyte (FABP4) OT3DKFOU FABP4_HUMAN Increases Expression [6]
Nitric oxide synthase 3 (NOS3) OTLDT7NR NOS3_HUMAN Increases Phosphorylation [7]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Increases Phosphorylation [7]
Peroxisome proliferator-activated receptor gamma (PPARG) OTHMARHO PPARG_HUMAN Increases Activity [6]
Peroxisome proliferator-activated receptor alpha (PPARA) OTK095PP PPARA_HUMAN Affects Binding [8]
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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 [9]
GABA transporter GAT-1 (SLC6A1) TTPRKM0 SC6A1_HUMAN Inhibitor [10]
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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 [11]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Metabolism [12]
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Tiagabine Interacts with 2 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Aromatase (CYP19A1) OTZ6XF74 CP19A_HUMAN Decreases Activity [13]
Sodium- and chloride-dependent GABA transporter 1 (SLC6A1) OTLCJJF3 SC6A1_HUMAN Decreases Activity [14]
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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: 2691).
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 Keratinocyte-derived vascular endothelial growth factor biosynthesis represents a pleiotropic side effect of peroxisome proliferator-activated receptor-gamma agonist troglitazone but not rosiglitazone and involves activation of p38 mitogen-activated protein kinase: implications for diabetes-impaired skin repair. Mol Pharmacol. 2008 Oct;74(4):952-63. doi: 10.1124/mol.108.049395. Epub 2008 Jul 3.
5 Novel peroxisome proliferator-activated receptor (PPAR) gamma and PPARdelta ligands produce distinct biological effects. J Biol Chem. 1999 Mar 5;274(10):6718-25.
6 Human adipocyte fatty acid-binding protein (aP2) gene promoter-driven reporter assay discriminates nonlipogenic peroxisome proliferator-activated receptor gamma ligands. J Pharmacol Exp Ther. 2004 Nov;311(2):467-75. doi: 10.1124/jpet.104.068254. Epub 2004 Jul 23.
7 Endothelium-dependent vasodilator effects of peroxisome proliferator-activated receptor beta agonists via the phosphatidyl-inositol-3 kinase-Akt pathway. J Pharmacol Exp Ther. 2010 Feb;332(2):554-61. doi: 10.1124/jpet.109.159806. Epub 2009 Nov 11.
8 Fibrate and statin synergistically increase the transcriptional activities of PPARalpha/RXRalpha and decrease the transactivation of NFkappaB. Biochem Biophys Res Commun. 2002 Jan 11;290(1):131-9. doi: 10.1006/bbrc.2001.6141.
9 Glutamate- and GABA-based CNS therapeutics. Curr Opin Pharmacol. 2006 Feb;6(1):7-17.
10 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).
11 Enzyme induction and inhibition by new antiepileptic drugs: a review of human studies. Fundam Clin Pharmacol. 2000 Jul-Aug;14(4):301-19.
12 Actual and Predicted Pharmacokinetic Interactions Between Anticonvulsants and Antiretrovirals.
13 Inhibition of human aromatase complex (CYP19) by antiepileptic drugs. Toxicol In Vitro. 2008 Feb;22(1):146-53.
14 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.