Details of the Drug Combination

General Information of Drug Combination (ID: DCRPS5V)

Drug Combination Name
Nitisinone Tiagabine
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Nitisinone   DMVS9WQ Tiagabine   DMKSQG0
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: KBM-7
Zero Interaction Potency (ZIP) Score: 10.59
Bliss Independence Score: 10.59
Loewe Additivity Score: 12.74
LHighest Single Agent (HSA) Score: 12.76

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Nitisinone
Disease Entry ICD 11 Status REF
Hereditary tyrosinemia type 1 5C50.11 Approved [2]
Nitisinone Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Hydroxyphenylpyruvate dioxygenase (HPD) TT8DSFC HPPD_HUMAN Inhibitor [4]
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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 [5]
GABA transporter GAT-1 (SLC6A1) TTPRKM0 SC6A1_HUMAN Inhibitor [6]
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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 [7]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Metabolism [8]
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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 [9]
Sodium- and chloride-dependent GABA transporter 1 (SLC6A1) OTLCJJF3 SC6A1_HUMAN Decreases Activity [10]
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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: 6834).
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 Experience of nitisinone for the pharmacological treatment of hereditary tyrosinaemia type 1. Expert Opin Pharmacother. 2008 May;9(7):1229-36.
5 Glutamate- and GABA-based CNS therapeutics. Curr Opin Pharmacol. 2006 Feb;6(1):7-17.
6 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).
7 Enzyme induction and inhibition by new antiepileptic drugs: a review of human studies. Fundam Clin Pharmacol. 2000 Jul-Aug;14(4):301-19.
8 Actual and Predicted Pharmacokinetic Interactions Between Anticonvulsants and Antiretrovirals.
9 Inhibition of human aromatase complex (CYP19) by antiepileptic drugs. Toxicol In Vitro. 2008 Feb;22(1):146-53.
10 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.