General Information of Drug Combination (ID: DCQT3VK)

Drug Combination Name
Trifluoperazine Sertraline
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Trifluoperazine   DMKBYWI Sertraline   DM0FB1J
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: 27.77
Bliss Independence Score: 27.77
Loewe Additivity Score: 41.82
LHighest Single Agent (HSA) Score: 41.82

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Trifluoperazine
Disease Entry ICD 11 Status REF
Anxiety N.A. Approved [2]
Schizophrenia 6A20 Approved [3]
Trifluoperazine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Calmodulin (CALM) TTV3NH6 CALM1_HUMAN; CALM2_HUMAN; CALM3_HUMAN Inhibitor [7]
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Trifluoperazine Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [8]
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Trifluoperazine Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [9]
Dimethylaniline oxidase 2 (FMO2) DEIASEZ FMO2_HUMAN Metabolism [10]
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Trifluoperazine Interacts with 7 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Flavin-containing monooxygenase 2 (FMO2) OTUJUL9S FMO2_HUMAN Increases Oxidation [10]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Activity [11]
E3 ubiquitin-protein ligase parkin (PRKN) OTJBN41W PRKN_HUMAN Affects Localization [12]
Stonin-2 (STON2) OT01JHHE STON2_HUMAN Decreases Expression [13]
D(3) dopamine receptor (DRD3) OT0OFFKB DRD3_HUMAN Increases ADR [14]
D(4) dopamine receptor (DRD4) OTAJTO7N DRD4_HUMAN Increases ADR [14]
D(2) dopamine receptor (DRD2) OTBLXKEG DRD2_HUMAN Increases ADR [14]
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⏷ Show the Full List of 7 DOT(s)
Indication(s) of Sertraline
Disease Entry ICD 11 Status REF
Coronary heart disease BA80.Z Approved [4]
Depression 6A70-6A7Z Approved [5]
Epilepsy 8A60-8A68 Approved [4]
Obsessive compulsive disorder 6B20 Approved [4]
Panic disorder 6B01 Approved [4]
Post-traumatic stress disorder 6B40 Approved [4]
Sertraline Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Serotonin transporter (SERT) TT3ROYC SC6A4_HUMAN Inhibitor [19]
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Sertraline Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [20]
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Sertraline Interacts with 7 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [21]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [22]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [23]
Cytochrome P450 2E1 (CYP2E1) DEVDYN7 CP2E1_HUMAN Metabolism [24]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [25]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Metabolism [26]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [26]
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⏷ Show the Full List of 7 DME(s)
Sertraline Interacts with 55 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 2C19 (CYP2C19) OTFMJYYE CP2CJ_HUMAN Decreases Methylation [27]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Activity [28]
Phytanoyl-CoA dioxygenase, peroxisomal (PHYH) OTUG4BWA PAHX_HUMAN Increases Expression [15]
Nuclear protein 1 (NUPR1) OT4FU8C0 NUPR1_HUMAN Increases Expression [15]
Alpha-1-antichymotrypsin (SERPINA3) OT9BP2S0 AACT_HUMAN Increases Expression [15]
Solute carrier family 2, facilitated glucose transporter member 3 (SLC2A3) OT2HZK5M GTR3_HUMAN Decreases Expression [15]
Inhibin beta E chain (INHBE) OTOI2NYG INHBE_HUMAN Increases Expression [15]
Acid ceramidase (ASAH1) OT1DNGXL ASAH1_HUMAN Increases Expression [15]
Nuclear receptor subfamily 0 group B member 2 (NR0B2) OT7UVICX NR0B2_HUMAN Increases Expression [15]
Lysophospholipase D GDPD3 (GDPD3) OTOHM9QM GDPD3_HUMAN Increases Expression [15]
Fibronectin type III domain-containing protein 4 (FNDC4) OTOQK0WK FNDC4_HUMAN Increases Expression [15]
Protein DEPP1 (DEPP1) OTB36PHJ DEPP1_HUMAN Increases Expression [15]
Mitogen-activated protein kinase kinase kinase 13 (MAP3K13) OTS93BTX M3K13_HUMAN Increases Expression [16]
Growth arrest and DNA damage-inducible protein GADD45 beta (GADD45B) OTL9I7LO GA45B_HUMAN Increases Expression [16]
Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1) OTY9R6FZ ERN1_HUMAN Increases Expression [16]
Protein phosphatase 1 regulatory subunit 15A (PPP1R15A) OTYG179K PR15A_HUMAN Increases Expression [16]
Dual specificity protein phosphatase 14 (DUSP14) OTGODFCR DUS14_HUMAN Increases Expression [16]
Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) OTBMJUOC M4K4_HUMAN Decreases Expression [16]
Protein c-Fos (FOS) OTJBUVWS FOS_HUMAN Increases Expression [16]
Myc proto-oncogene protein (MYC) OTPV5LUK MYC_HUMAN Increases Expression [16]
Albumin (ALB) OTVMM513 ALBU_HUMAN Affects Binding [29]
Platelet basic protein (PPBP) OT1FHGQS CXCL7_HUMAN Decreases Expression [30]
Eukaryotic translation initiation factor 2 subunit 1 (EIF2S1) OTM0GDTP IF2A_HUMAN Increases Phosphorylation [16]
Transcription factor Jun (JUN) OTCYBO6X JUN_HUMAN Increases Expression [16]
Transcription factor AP-2-alpha (TFAP2A) OTMYT3NK AP2A_HUMAN Increases Expression [31]
Heat shock cognate 71 kDa protein (HSPA8) OTJI2RCI HSP7C_HUMAN Decreases Expression [16]
Cyclic AMP-dependent transcription factor ATF-2 (ATF2) OTNIZPEA ATF2_HUMAN Increases Expression [16]
Heat shock 70 kDa protein 6 (HSPA6) OTH4S7WB HSP76_HUMAN Increases Expression [16]
Transcription factor JunD (JUND) OTNKACJD JUND_HUMAN Increases Expression [16]
Cyclic AMP-dependent transcription factor ATF-4 (ATF4) OTRFV19J ATF4_HUMAN Increases Expression [16]
Nuclear factor NF-kappa-B p105 subunit (NFKB1) OTNRRD8I NFKB1_HUMAN Increases Expression [16]
Growth arrest and DNA damage-inducible protein GADD45 alpha (GADD45A) OTDRV63V GA45A_HUMAN Increases Expression [16]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Increases Phosphorylation [32]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Increases Phosphorylation [32]
DNA damage-inducible transcript 3 protein (DDIT3) OTI8YKKE DDIT3_HUMAN Increases Expression [16]
Mitogen-activated protein kinase kinase kinase 8 (MAP3K8) OTOZTA1F M3K8_HUMAN Increases Expression [16]
Translocon-associated protein subunit beta (SSR2) OTQJSL7M SSRB_HUMAN Increases Expression [16]
Protein transport protein Sec61 subunit gamma (SEC61G) OT7MJRXY SC61G_HUMAN Decreases Expression [16]
E3 ubiquitin-protein ligase RBX1 (RBX1) OTYA1UIO RBX1_HUMAN Decreases Expression [16]
S-phase kinase-associated protein 1 (SKP1) OT5BPAZ4 SKP1_HUMAN Decreases Expression [16]
Nuclear factor NF-kappa-B p100 subunit (NFKB2) OTS231V7 NFKB2_HUMAN Increases Expression [16]
Transcription factor RelB (RELB) OTU3QYEF RELB_HUMAN Increases Expression [16]
Acetyl-CoA carboxylase 1 (ACACA) OT5CQPZY ACACA_HUMAN Increases Phosphorylation [18]
Dual specificity protein phosphatase 8 (DUSP8) OTPLMPG9 DUS8_HUMAN Increases Expression [16]
Cullin-1 (CUL1) OTXPE1UZ CUL1_HUMAN Decreases Expression [16]
Homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 1 protein (HERPUD1) OT9EROL6 HERP1_HUMAN Increases Expression [16]
Serine/threonine-protein kinase STK11 (STK11) OT1YZSP3 STK11_HUMAN Increases Phosphorylation [18]
E3 ubiquitin-protein ligase synoviolin (SYVN1) OTZ4ZJP5 SYVN1_HUMAN Increases Expression [16]
Dual specificity protein phosphatase 16 (DUSP16) OTK7S078 DUS16_HUMAN Increases Expression [16]
Microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B) OTUYHB84 MLP3B_HUMAN Increases Lipidation [18]
DnaJ homolog subfamily C member 5 (DNAJC5) OTCZDXAL DNJC5_HUMAN Increases Expression [33]
Eukaryotic translation initiation factor 2-alpha kinase 3 (EIF2AK3) OT0DZGY4 E2AK3_HUMAN Increases Expression [16]
Serine/threonine-protein kinase TAO2 (TAOK2) OTNUMOZ1 TAOK2_HUMAN Increases Expression [16]
C-Jun-amino-terminal kinase-interacting protein 3 (MAPK8IP3) OT0X8ACY JIP3_HUMAN Increases Expression [16]
Sodium-dependent serotonin transporter (SLC6A4) OT6FGDLW SC6A4_HUMAN Increases Response To Substance [34]
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⏷ Show the Full List of 55 DOT(s)

References

1 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
2 Trifluoperazine FDA Label
3 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
4 Sertraline FDA Label
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: 4798).
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10 Human FMO2-based microbial whole-cell catalysts for drug metabolite synthesis. Microb Cell Fact. 2015 Jun 12;14:82.
11 Characterization of the ATPase activity of the Mr 170,000 to 180,000 membrane glycoprotein (P-glycoprotein) associated with multidrug resistance in K562/ADM cells. Cancer Res. 1988 Sep 1;48(17):4926-32.
12 Rescue of Pink1 Deficiency by Stress-Dependent Activation of Autophagy. Cell Chem Biol. 2017 Apr 20;24(4):471-480.e4. doi: 10.1016/j.chembiol.2017.03.005. Epub 2017 Mar 30.
13 Stonin 2 activates lysosomal-mTOR axis for cell survival in oral cancer. Toxicol In Vitro. 2023 Apr;88:105561. doi: 10.1016/j.tiv.2023.105561. Epub 2023 Jan 23.
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15 A toxicogenomic approach to drug-induced phospholipidosis: analysis of its induction mechanism and establishment of a novel in vitro screening system. Toxicol Sci. 2005 Feb;83(2):282-92.
16 Sertraline induces endoplasmic reticulum stress in hepatic cells. Toxicology. 2014 Aug 1;322:78-88. doi: 10.1016/j.tox.2014.05.007. Epub 2014 May 24.
17 Relationship between release of platelet/endothelial biomarkers and plasma levels of sertraline and N-desmethylsertraline in acute coronary syndrome patients receiving SSRI treatment for depression. Am J Psychiatry. 2005 Jun;162(6):1165-70. doi: 10.1176/appi.ajp.162.6.1165.
18 Antidepressant drug sertraline modulates AMPK-MTOR signaling-mediated autophagy via targeting mitochondrial VDAC1 protein. Autophagy. 2021 Oct;17(10):2783-2799. doi: 10.1080/15548627.2020.1841953. Epub 2020 Nov 9.
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21 New orally active anticoagulant agents for the prevention and treatment of venous thromboembolism in cancer patients. Ther Clin Risk Manag. 2014 Jun 13;10:423-36.
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23 Some aspects of genetic polymorphism in the biotransformation of antidepressants. Therapie. 2004 Jan-Feb;59(1):5-12.
24 PharmGKB: A worldwide resource for pharmacogenomic information. Wiley Interdiscip Rev Syst Biol Med. 2018 Jul;10(4):e1417. (ID: PA166181117)
25 Sertraline is metabolized by multiple cytochrome P450 enzymes, monoamine oxidases, and glucuronyl transferases in human: an in vitro study. Drug Metab Dispos. 2005 Feb;33(2):262-70.
26 Influence of CYP2B6 and CYP2C19 polymorphisms on sertraline metabolism in major depression patients. Int J Clin Pharm. 2016 Apr;38(2):388-94.
27 Pharmacokinetics of sertraline in relation to genetic polymorphism of CYP2C19. Clin Pharmacol Ther. 2001 Jul;70(1):42-7.
28 Michaelis-Menten kinetic analysis of drugs of abuse to estimate their affinity to human P-glycoprotein. Toxicol Lett. 2013 Feb 27;217(2):137-42. doi: 10.1016/j.toxlet.2012.12.012. Epub 2012 Dec 27.
29 Exploring binding properties of sertraline with human serum albumin: Combination of spectroscopic and molecular modeling studies. Chem Biol Interact. 2015 Dec 5;242:235-46. doi: 10.1016/j.cbi.2015.10.006. Epub 2015 Oct 22.
30 Platelet/endothelial biomarkers in depressed patients treated with the selective serotonin reuptake inhibitor sertraline after acute coronary events: the Sertraline AntiDepressant Heart Attack Randomized Trial (SADHART) Platelet Substudy. Circulation. 2003 Aug 26;108(8):939-44. doi: 10.1161/01.CIR.0000085163.21752.0A. Epub 2003 Aug 11.
31 Impact of selective serotonin reuptake inhibitors on neural crest stem cell formation. Toxicol Lett. 2017 Nov 5;281:20-25. doi: 10.1016/j.toxlet.2017.08.012. Epub 2017 Aug 24.
32 Sertraline, an antidepressant, induces apoptosis in hepatic cells through the mitogen-activated protein kinase pathway. Toxicol Sci. 2014 Feb;137(2):404-15. doi: 10.1093/toxsci/kft254. Epub 2013 Nov 5.
33 Induction of cysteine string protein after chronic antidepressant treatment in rat frontal cortex. Neurosci Lett. 2001 Apr 6;301(3):183-6. doi: 10.1016/s0304-3940(01)01638-x.
34 The serotonin transporter polymorphism, 5HTTLPR, is associated with a faster response time to sertraline in an elderly population with major depressive disorder. Psychopharmacology (Berl). 2004 Aug;174(4):525-9. doi: 10.1007/s00213-003-1562-3. Epub 2003 Sep 4.