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 19 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Serine protease HTRA2, mitochondrial (HTRA2) OTC7616F HTRA2_HUMAN Affects Localization [4]
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Increases Secretion [5]
Interferon gamma (IFNG) OTXG9JM7 IFNG_HUMAN Increases Secretion [5]
C-X-C motif chemokine 10 (CXCL10) OTTLQ6S0 CXL10_HUMAN Decreases Secretion [5]
Interleukin-5 (IL5) OTAFPSCO IL5_HUMAN Decreases Secretion [5]
Transcription factor Sp1 (SP1) OTISPT4X SP1_HUMAN Increases Activity [6]
Heme oxygenase 1 (HMOX1) OTC1W6UX HMOX1_HUMAN Increases Expression [7]
C-C motif chemokine 5 (CCL5) OTSCA5CK CCL5_HUMAN Decreases Secretion [5]
Cystic fibrosis transmembrane conductance regulator (CFTR) OT6B22QH CFTR_HUMAN Decreases Expression [6]
Interleukin-10 (IL10) OTIRFRXC IL10_HUMAN Decreases Secretion [5]
Interleukin-12 subunit beta (IL12B) OT0JF8A3 IL12B_HUMAN Decreases Expression [5]
T-lymphocyte activation antigen CD86 (CD86) OTJCSBPC CD86_HUMAN Decreases Expression [5]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [4]
Transcription factor Sp3 (SP3) OTYDQZ1T SP3_HUMAN Decreases Activity [6]
Caspase-8 (CASP8) OTA8TVI8 CASP8_HUMAN Increases Activity [4]
Hypoxia-inducible factor 1-alpha (HIF1A) OTADSC03 HIF1A_HUMAN Increases Expression [8]
Carbonyl reductase 1 (CBR1) OTQ3A541 CBR1_HUMAN Increases Reduction [9]
Serine-protein kinase ATM (ATM) OTQVOHLT ATM_HUMAN Increases Response To Substance [10]
Alcohol dehydrogenase class-3 (ADH5) OTSO67MI ADHX_HUMAN Increases Reduction [11]
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⏷ Show the Full List of 19 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 [12]
5-HT 1A receptor (HTR1A) TTSQIFT 5HT1A_HUMAN Modulator [12]
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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 [13]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [14]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [15]
Cytochrome P450 3A7 (CYP3A7) DERD86B CP3A7_HUMAN Metabolism [15]
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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 [16]
5-hydroxytryptamine receptor 1A (HTR1A) OT38K9MK 5HT1A_HUMAN Affects Binding [17]
5-hydroxytryptamine receptor 2C (HTR2C) OT6H8DE0 5HT2C_HUMAN Affects Binding [18]
Proepiregulin (EREG) OTRM4NQY EREG_HUMAN Increases Expression [19]
Interleukin-1 alpha (IL1A) OTPSGILV IL1A_HUMAN Increases Expression [19]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Increases Expression [19]
Antileukoproteinase (SLPI) OTUNFUU8 SLPI_HUMAN Increases Expression [19]
Hepatocyte growth factor receptor (MET) OT7K55MU MET_HUMAN Increases Expression [19]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [19]
Bone morphogenetic protein 6 (BMP6) OT9WN536 BMP6_HUMAN Increases Expression [19]
Prostaglandin G/H synthase 2 (PTGS2) OT75U9M4 PGH2_HUMAN Increases Expression [19]
Tumor necrosis factor-inducible gene 6 protein (TNFAIP6) OT1SLUZH TSG6_HUMAN Increases Expression [19]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [20]
Interleukin-24 (IL24) OT4VUWH1 IL24_HUMAN Increases Expression [19]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Decreases Activity [21]
PTB-containing, cubilin and LRP1-interacting protein (PID1) OT5YJ7FI PCLI1_HUMAN Increases Expression [19]
Cystine/glutamate transporter (SLC7A11) OTKJ6PXW XCT_HUMAN Increases Expression [19]
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⏷ Show the Full List of 17 DOT(s)

References

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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 Induction of heme oxygenase-1 as a response in sensing the signals evoked by distinct nitric oxide donors. Biochem Pharmacol. 1999 Jul 15;58(2):227-36. doi: 10.1016/s0006-2952(99)00097-0.
8 Regulation of the hypoxia-inducible factor 1alpha by the inflammatory mediators nitric oxide and tumor necrosis factor-alpha in contrast to desferroxamine and phenylarsine oxide. J Biol Chem. 2001 Oct 26;276(43):39805-11. doi: 10.1074/jbc.M107689200. Epub 2001 Aug 20.
9 Studies on reduction of S-nitrosoglutathione by human carbonyl reductases 1 and 3. Chem Biol Interact. 2011 May 30;191(1-3):95-103.
10 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.
11 The Janus face of alcohol dehydrogenase 3. Chem Biol Interact. 2009 Mar 16;178(1-3):29-35. doi: 10.1016/j.cbi.2008.10.050. Epub 2008 Nov 6.
12 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
13 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.
14 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.
15 Drug Interactions Flockhart Table
16 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.
17 Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. doi: 10.1007/BF02244985.
18 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.
19 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.
20 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.
21 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.