Details of the Drug Combination

General Information of Drug Combination (ID: DCWWI44)

Drug Combination Name
Mebutamate Trazodone
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Mebutamate   DM0KYI4 Trazodone   DMK1GBJ
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: 0.26
Bliss Independence Score: 0.26
Loewe Additivity Score: 13.5
LHighest Single Agent (HSA) Score: 13.5

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Mebutamate
Disease Entry ICD 11 Status REF
Anxiety disorder 6B00-6B0Z Approved [2]
Mebutamate Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
GABA(A) receptor gamma-3 (GABRG3) TTEX6LM GBRG3_HUMAN Modulator [4]
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Indication(s) of Trazodone
Disease Entry ICD 11 Status REF
Depression 6A70-6A7Z Approved [3]
Trazodone Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Serotonin transporter (SERT) TT3ROYC SC6A4_HUMAN Modulator [4]
5-HT 1A receptor (HTR1A) TTSQIFT 5HT1A_HUMAN Modulator [4]
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Trazodone Interacts with 4 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [5]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [6]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [7]
Cytochrome P450 3A7 (CYP3A7) DERD86B CP3A7_HUMAN Metabolism [7]
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Trazodone Interacts with 17 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 2D6 (CYP2D6) OTZJC802 CP2D6_HUMAN Increases ADR [8]
5-hydroxytryptamine receptor 1A (HTR1A) OT38K9MK 5HT1A_HUMAN Affects Binding [9]
5-hydroxytryptamine receptor 2C (HTR2C) OT6H8DE0 5HT2C_HUMAN Affects Binding [10]
Proepiregulin (EREG) OTRM4NQY EREG_HUMAN Increases Expression [11]
Interleukin-1 alpha (IL1A) OTPSGILV IL1A_HUMAN Increases Expression [11]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Increases Expression [11]
Antileukoproteinase (SLPI) OTUNFUU8 SLPI_HUMAN Increases Expression [11]
Hepatocyte growth factor receptor (MET) OT7K55MU MET_HUMAN Increases Expression [11]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [11]
Bone morphogenetic protein 6 (BMP6) OT9WN536 BMP6_HUMAN Increases Expression [11]
Prostaglandin G/H synthase 2 (PTGS2) OT75U9M4 PGH2_HUMAN Increases Expression [11]
Tumor necrosis factor-inducible gene 6 protein (TNFAIP6) OT1SLUZH TSG6_HUMAN Increases Expression [11]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [12]
Interleukin-24 (IL24) OT4VUWH1 IL24_HUMAN Increases Expression [11]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Decreases Activity [13]
PTB-containing, cubilin and LRP1-interacting protein (PID1) OT5YJ7FI PCLI1_HUMAN Increases Expression [11]
Cystine/glutamate transporter (SLC7A11) OTKJ6PXW XCT_HUMAN Increases Expression [11]
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⏷ Show the Full List of 17 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: 213).
4 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
5 Metabolic activation of the nontricyclic antidepressant trazodone to electrophilic quinone-imine and epoxide intermediates in human liver microsomes and recombinant P4503A4. Chem Biol Interact. 2005 Jun 30;155(1-2):10-20.
6 Evaluating the role of drug metabolism and reactive intermediates in trazodone-induced cytotoxicity toward freshly-isolated rat hepatocytes. Drug Res (Stuttg). 2016 Nov;66(11):592-596.
7 Drug Interactions Flockhart Table
8 ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
9 Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. doi: 10.1007/BF02244985.
10 Inverse agonist and neutral antagonist actions of antidepressants at recombinant and native 5-hydroxytryptamine2C receptors: differential modulatio... Mol Pharmacol. 2008 Mar;73(3):748-57.
11 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.
12 Effect of trazodone on hERG channel current and QT-interval. Eur J Pharmacol. 2005 Mar 7;510(1-2):75-85. doi: 10.1016/j.ejphar.2005.01.009.
13 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.