Details of the Drug Combination

General Information of Drug Combination (ID: DC9D5SW)

Drug Combination Name
Trihexyphenidyl Dronedarone
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Trihexyphenidyl   DMB19L8 Dronedarone   DMA8FS5
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: 0.79
Bliss Independence Score: 0.79
Loewe Additivity Score: 14.8
LHighest Single Agent (HSA) Score: 14.81

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Trihexyphenidyl
Disease Entry ICD 11 Status REF
Dystonia 8A02 Approved [2]
Parkinson disease 8A00.0 Approved [2]
Parkinsonian disorder N.A. Approved [3]
Postencephalitic Parkinson disease N.A. Approved [3]
Obesity 5B81 Investigative [4]
Trihexyphenidyl Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Muscarinic acetylcholine receptor M1 (CHRM1) TTZ9SOR ACM1_HUMAN Antagonist [6]
Adrenergic receptor beta-3 (ADRB3) TTMXGCW ADRB3_HUMAN Agonist [4]
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Trihexyphenidyl Interacts with 6 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Proepiregulin (EREG) OTRM4NQY EREG_HUMAN Increases Expression [7]
Antileukoproteinase (SLPI) OTUNFUU8 SLPI_HUMAN Increases Expression [7]
Hepatocyte growth factor receptor (MET) OT7K55MU MET_HUMAN Increases Expression [7]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [7]
Tumor necrosis factor-inducible gene 6 protein (TNFAIP6) OT1SLUZH TSG6_HUMAN Increases Expression [7]
PTB-containing, cubilin and LRP1-interacting protein (PID1) OT5YJ7FI PCLI1_HUMAN Increases Expression [7]
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⏷ Show the Full List of 6 DOT(s)
Indication(s) of Dronedarone
Disease Entry ICD 11 Status REF
Angina pectoris BA40 Approved [5]
Atrial fibrillation BC81.3 Withdrawn from market [5]
Dronedarone Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Voltage-gated potassium channel Kv1.5 (KCNA5) TTW0CMT KCNA5_HUMAN Blocker [8]
Potassium channel unspecific (KC) TT1VOHK NOUNIPROTAC Inhibitor [9]
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Dronedarone Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [10]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [11]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [12]
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Dronedarone Interacts with 4 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Superoxide dismutase , mitochondrial (SOD2) OTIWXGZ9 SODM_HUMAN Increases Expression [13]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Phosphorylation [14]
G1/S-specific cyclin-D3 (CCND3) OTNKPQ22 CCND3_HUMAN Decreases Expression [14]
Cytochrome P450 2C19 (CYP2C19) OTFMJYYE CP2CJ_HUMAN Increases Metabolism [14]
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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: 7315).
3 Trihexyphenidyl FDA Label
4 Obesity: pathophysiology and clinical management. Curr Med Chem. 2009;16(4):506-21.
5 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: 7465).
6 The role of M1 muscarinic cholinergic receptors in the discriminative stimulus properties of N-desmethylclozapine and the atypical antipsychotic dr... Psychopharmacology (Berl). 2009 Apr;203(2):295-301.
7 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.
8 New antiarrhythmic agents for atrial fibrillation and atrial flutter. Expert Opin Emerg Drugs. 2005 May;10(2):311-22.
9 Antibodies and venom peptides: new modalities for ion channels. Nat Rev Drug Discov. 2019 May;18(5):339-357.
10 Drug safety evaluation of dronedarone in atrial fibrillation. Expert Opin Drug Saf. 2012 Nov;11(6):1023-45.
11 Effect of dronedarone on the pharmacokinetics of carvedilol following oral administration to rats. Eur J Pharm Sci. 2018 Jan 1;111:13-19.
12 Inactivation of human cytochrome P450 3A4 and 3A5 by dronedarone and N-desbutyl dronedarone. Mol Pharmacol. 2016 Jan;89(1):1-13.
13 Mechanisms of hepatocellular toxicity associated with dronedarone--a comparison to amiodarone. Toxicol Sci. 2013 Feb;131(2):480-90. doi: 10.1093/toxsci/kfs298. Epub 2012 Nov 7.
14 The role of hepatic cytochrome P450s in the cytotoxicity of dronedarone. Arch Toxicol. 2018 Jun;92(6):1969-1981. doi: 10.1007/s00204-018-2196-x. Epub 2018 Apr 3.