Details of the Drug Combination

General Information of Drug Combination (ID: DCJRM94)

Drug Combination Name
Fluspirilene Entacapone
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Fluspirilene   DMFO843 Entacapone   DMLBVKQ
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: 7.01
Bliss Independence Score: 7.01
Loewe Additivity Score: 21.54
LHighest Single Agent (HSA) Score: 21.54

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Fluspirilene
Disease Entry ICD 11 Status REF
Schizophrenia 6A20 Approved [2]
Fluspirilene Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Dopamine D2 receptor (D2R) TTEX248 DRD2_HUMAN Antagonist [4]
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Fluspirilene Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [5]
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Indication(s) of Entacapone
Disease Entry ICD 11 Status REF
Parkinson disease 8A00.0 Approved [3]
Entacapone Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Catechol-O-methyl-transferase (COMT) TTKWFB8 COMT_HUMAN Inhibitor [8]
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Entacapone Interacts with 2 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [9]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [10]
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Entacapone Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
UDP-glucuronosyltransferase 1A9 (UGT1A9) DE85D2P UD19_HUMAN Metabolism [7]
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Entacapone Interacts with 12 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Glycerol-3-phosphate acyltransferase 1, mitochondrial (GPAM) OTR1XD9B GPAT1_HUMAN Decreases Expression [11]
Proepiregulin (EREG) OTRM4NQY EREG_HUMAN Increases Expression [12]
Interleukin-1 alpha (IL1A) OTPSGILV IL1A_HUMAN Increases Expression [12]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Increases Expression [12]
Antileukoproteinase (SLPI) OTUNFUU8 SLPI_HUMAN Decreases Expression [12]
Hepatocyte growth factor receptor (MET) OT7K55MU MET_HUMAN Increases Expression [12]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [12]
Catechol O-methyltransferase (COMT) OTPWKTQG COMT_HUMAN Decreases Activity [13]
Prostaglandin G/H synthase 2 (PTGS2) OT75U9M4 PGH2_HUMAN Increases Expression [12]
Tumor necrosis factor-inducible gene 6 protein (TNFAIP6) OT1SLUZH TSG6_HUMAN Decreases Expression [12]
PTB-containing, cubilin and LRP1-interacting protein (PID1) OT5YJ7FI PCLI1_HUMAN Decreases Expression [12]
Cystine/glutamate transporter (SLC7A11) OTKJ6PXW XCT_HUMAN Decreases Expression [12]
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⏷ Show the Full List of 12 DOT(s)

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: 85).
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: 6647).
4 Inhibition of glutamate release by fluspirilene in cerebrocortical nerve terminals (synaptosomes). Synapse. 2002 Apr;44(1):36-41.
5 Integrated analysis on the physicochemical properties of dihydropyridine calcium channel blockers in grapefruit juice interactions. Curr Pharm Biotechnol. 2012 Jul;13(9):1705-17.
6 Two patients with COMT inhibitor-induced hepatic dysfunction and UGT1A9 genetic polymorphism. Neurology. 2005 Dec 13;65(11):1820-2. doi: 10.1212/01.wnl.0000187066.81162.70.
7 Kinetic characterization of the 1A subfamily of recombinant human UDP-glucuronosyltransferases. Drug Metab Dispos. 2005 Jul;33(7):1017-26.
8 Entacapone: a catechol-O-methyltransferase inhibitor for the adjunctive treatment of Parkinson's disease. Clin Ther. 2001 Jun;23(6):802-32; discussion 771.
9 Elucidation of the Impact of P-glycoprotein and Breast Cancer Resistance Protein on the Brain Distribution of Catechol-O-Methyltransferase Inhibitors. Drug Metab Dispos. 2017 Dec;45(12):1282-1291.
10 Organic Anion Transporter 2-Mediated Hepatic Uptake Contributes to the Clearance of High-Permeability-Low-Molecular-Weight Acid and Zwitterion Drugs: Evaluation Using 25 Drugs. J Pharmacol Exp Ther. 2018 Nov;367(2):322-334.
11 Effect of the Catechol-O-Methyltransferase Inhibitors Tolcapone and Entacapone on Fatty Acid Metabolism in HepaRG Cells. Toxicol Sci. 2018 Aug 1;164(2):477-488.
12 An in vitro coculture system of human peripheral blood mononuclear cells with hepatocellular carcinoma-derived cells for predicting drug-induced liver injury. Arch Toxicol. 2021 Jan;95(1):149-168. doi: 10.1007/s00204-020-02882-4. Epub 2020 Aug 20.
13 Beneficial effects of natural phenolics on levodopa methylation and oxidative neurodegeneration. Brain Res. 2013 Feb 25;1497:1-14. doi: 10.1016/j.brainres.2012.11.043. Epub 2012 Dec 1.