Details of the Drug Combination

General Information of Drug Combination (ID: DCE44R7)

Drug Combination Name
Nitrosoglutathione Trazodone
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Nitrosoglutathione   DMZ9WI4 Trazodone   DMK1GBJ
N.A. 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: 8.84
Bliss Independence Score: 8.84
Loewe Additivity Score: 21.8
LHighest Single Agent (HSA) Score: 21.8

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Nitrosoglutathione Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
S-(hydroxymethyl)glutathione dehydrogenase (adh) DEAH3PE A0A0A7DS01_VIBCL Metabolism [3]
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Nitrosoglutathione Interacts with 6 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Serine protease HTRA2, mitochondrial (HTRA2) OTC7616F HTRA2_HUMAN Affects Localization [4]
C-C motif chemokine 5 (CCL5) OTSCA5CK CCL5_HUMAN Decreases Secretion [5]
Interleukin-12 subunit beta (IL12B) OT0JF8A3 IL12B_HUMAN Decreases Expression [5]
Transcription factor Sp3 (SP3) OTYDQZ1T SP3_HUMAN Decreases Activity [6]
Carbonyl reductase 1 (CBR1) OTQ3A541 CBR1_HUMAN Increases Reduction [7]
Serine-protein kinase ATM (ATM) OTQVOHLT ATM_HUMAN Increases Response To Substance [8]
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⏷ Show the Full List of 6 DOT(s)
Indication(s) of Trazodone
Disease Entry ICD 11 Status REF
Depression 6A70-6A7Z Approved [2]
Trazodone Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Serotonin transporter (SERT) TT3ROYC SC6A4_HUMAN Modulator [9]
5-HT 1A receptor (HTR1A) TTSQIFT 5HT1A_HUMAN Modulator [9]
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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 [10]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [11]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [12]
Cytochrome P450 3A7 (CYP3A7) DERD86B CP3A7_HUMAN Metabolism [12]
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Trazodone Interacts with 8 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
5-hydroxytryptamine receptor 1A (HTR1A) OT38K9MK 5HT1A_HUMAN Affects Binding [13]
5-hydroxytryptamine receptor 2C (HTR2C) OT6H8DE0 5HT2C_HUMAN Affects Binding [14]
Proepiregulin (EREG) OTRM4NQY EREG_HUMAN Increases Expression [15]
Antileukoproteinase (SLPI) OTUNFUU8 SLPI_HUMAN Increases Expression [15]
Hepatocyte growth factor receptor (MET) OT7K55MU MET_HUMAN Increases Expression [15]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [15]
Tumor necrosis factor-inducible gene 6 protein (TNFAIP6) OT1SLUZH TSG6_HUMAN Increases Expression [15]
PTB-containing, cubilin and LRP1-interacting protein (PID1) OT5YJ7FI PCLI1_HUMAN Increases Expression [15]
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⏷ Show the Full List of 8 DOT(s)

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: 213).
3 Nitrosative stress response in Vibrio cholerae: role of S-nitrosoglutathione reductase. Appl Biochem Biotechnol. 2017 Jul;182(3):871-884.
4 The induction of reactive oxygen species and loss of mitochondrial Omi/HtrA2 is associated with S-nitrosoglutathione-induced apoptosis in human endothelial cells. Toxicol Appl Pharmacol. 2010 May 1;244(3):374-84. doi: 10.1016/j.taap.2010.02.004. Epub 2010 Feb 11.
5 Regulatory role of nitric oxide on monocyte-derived dendritic cell functions. J Interferon Cytokine Res. 2003 Aug;23(8):423-31. doi: 10.1089/107999003322277838.
6 Concentration-dependent effects of endogenous S-nitrosoglutathione on gene regulation by specificity proteins Sp3 and Sp1. Biochem J. 2004 May 15;380(Pt 1):67-74. doi: 10.1042/BJ20031687.
7 Studies on reduction of S-nitrosoglutathione by human carbonyl reductases 1 and 3. Chem Biol Interact. 2011 May 30;191(1-3):95-103.
8 Hypersensitivity of ataxia-telangiectasia fibroblasts to a nitric oxide donor. Free Radic Biol Med. 1997;22(1-2):343-7. doi: 10.1016/s0891-5849(96)00336-x.
9 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
10 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.
11 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.
12 Drug Interactions Flockhart Table
13 Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. doi: 10.1007/BF02244985.
14 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.
15 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.