General Information of Drug Combination (ID: DC352Z0)

Drug Combination Name
NABILONE Dronedarone
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs NABILONE   DMVRYT2 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: 0.93
Bliss Independence Score: 0.93
Loewe Additivity Score: 14.67
LHighest Single Agent (HSA) Score: 14.68

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of NABILONE
Disease Entry ICD 11 Status REF
Insomnia 7A00-7A0Z Approved [2]
NABILONE Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Cannabinoid receptor 2 (CB2) TTMSFAW CNR2_HUMAN Inhibitor [4]
Cannabinoid receptor 1 (CB1) TT6OEDT CNR1_HUMAN Inhibitor [4]
------------------------------------------------------------------------------------
NABILONE Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cannabinoid receptor 2 (CNR2) OTYP9P43 CNR2_HUMAN Affects Binding [5]
------------------------------------------------------------------------------------
Indication(s) of Dronedarone
Disease Entry ICD 11 Status REF
Angina pectoris BA40 Approved [3]
Atrial fibrillation BC81.3 Withdrawn from market [3]
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 [6]
Potassium channel unspecific (KC) TT1VOHK NOUNIPROTAC Inhibitor [7]
------------------------------------------------------------------------------------
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 [8]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [9]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [10]
------------------------------------------------------------------------------------
Dronedarone Interacts with 21 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Decreases Response To Substance [11]
Cytochrome P450 2D6 (CYP2D6) OTZJC802 CP2D6_HUMAN Decreases Response To Substance [11]
Cytochrome P450 3A5 (CYP3A5) OTSXFBXB CP3A5_HUMAN Decreases Response To Substance [11]
Superoxide dismutase , mitochondrial (SOD2) OTIWXGZ9 SODM_HUMAN Increases Expression [12]
DNA topoisomerase 2-alpha (TOP2A) OT6LPS08 TOP2A_HUMAN Decreases Expression [11]
Cyclin-dependent kinase 4 (CDK4) OT7EP05T CDK4_HUMAN Decreases Expression [11]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Phosphorylation [11]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Decreases Expression [11]
Cyclin-dependent kinase 2 (CDK2) OTB5DYYZ CDK2_HUMAN Decreases Expression [11]
G1/S-specific cyclin-D3 (CCND3) OTNKPQ22 CCND3_HUMAN Decreases Expression [11]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [12]
Caspase-7 (CASP7) OTAPJ040 CASP7_HUMAN Increases Activity [12]
Cyclin-dependent kinase 6 (CDK6) OTR95N0X CDK6_HUMAN Decreases Expression [11]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [13]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Decreases Activity [14]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Increases Metabolism [11]
Cytochrome P450 2C19 (CYP2C19) OTFMJYYE CP2CJ_HUMAN Increases Metabolism [11]
Cytochrome P450 2E1 (CYP2E1) OTHQ17JG CP2E1_HUMAN Increases Metabolism [11]
Cytochrome P450 2B6 (CYP2B6) OTOYO4S7 CP2B6_HUMAN Increases Metabolism [11]
Cytochrome P450 3A7 (CYP3A7) OTTCDHHM CP3A7_HUMAN Increases Metabolism [11]
Cytochrome P450 2C18 (CYP2C18) OTY687L9 CP2CI_HUMAN Increases Metabolism [11]
------------------------------------------------------------------------------------
⏷ Show the Full List of 21 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 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
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: 7465).
4 Novel 1',1'-chain substituted hexahydrocannabinols: 9-hydroxy-3-(1-hexyl-cyclobut-1-yl)-hexahydrocannabinol (AM2389) a highly potent cannabinoid r... J Med Chem. 2010 Oct 14;53(19):6996-7010.
5 Cloning and pharmacological characterization of the dog cannabinoid CB?receptor. Eur J Pharmacol. 2011 Nov 1;669(1-3):24-31. doi: 10.1016/j.ejphar.2011.08.002. Epub 2011 Aug 19.
6 New antiarrhythmic agents for atrial fibrillation and atrial flutter. Expert Opin Emerg Drugs. 2005 May;10(2):311-22.
7 Antibodies and venom peptides: new modalities for ion channels. Nat Rev Drug Discov. 2019 May;18(5):339-357.
8 Drug safety evaluation of dronedarone in atrial fibrillation. Expert Opin Drug Saf. 2012 Nov;11(6):1023-45.
9 Effect of dronedarone on the pharmacokinetics of carvedilol following oral administration to rats. Eur J Pharm Sci. 2018 Jan 1;111:13-19.
10 Inactivation of human cytochrome P450 3A4 and 3A5 by dronedarone and N-desbutyl dronedarone. Mol Pharmacol. 2016 Jan;89(1):1-13.
11 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.
12 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.
13 Five novel single nucleotide polymorphisms in the CYP2C8 gene, one of which induces a frame-shift. Drug Metab Pharmacokinet. 2002;17(4):374-7. doi: 10.2133/dmpk.17.374.
14 Association of CYP1A1 and CYP1B1 inhibition in in vitro assays with drug-induced liver injury. J Toxicol Sci. 2021;46(4):167-176. doi: 10.2131/jts.46.167.