Details of the Drug Combination

General Information of Drug Combination (ID: DCO3IIW)

Drug Combination Name
Sertraline Venlafaxine
Indication
Disease Entry Status REF
Depression Phase 1 [1]
Component Drugs Sertraline   DM0FB1J Venlafaxine   DMR6QH0
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Sertraline
Disease Entry ICD 11 Status REF
Coronary heart disease BA80.Z Approved [2]
Depression 6A70-6A7Z Approved [3]
Epilepsy 8A60-8A68 Approved [2]
Obsessive compulsive disorder 6B20 Approved [2]
Panic disorder 6B01 Approved [2]
Post-traumatic stress disorder 6B40 Approved [2]
Sertraline Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Serotonin transporter (SERT) TT3ROYC SC6A4_HUMAN Inhibitor [10]
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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 [11]
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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 [12]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [13]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [14]
Cytochrome P450 2E1 (CYP2E1) DEVDYN7 CP2E1_HUMAN Metabolism [15]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [16]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Metabolism [17]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [17]
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⏷ Show the Full List of 7 DME(s)
Sertraline Interacts with 88 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 2B6 (CYP2B6) OTOYO4S7 CP2B6_HUMAN Decreases Activity [18]
Cytochrome P450 2D6 (CYP2D6) OTZJC802 CP2D6_HUMAN Increases ADR [19]
Cytochrome P450 2C19 (CYP2C19) OTFMJYYE CP2CJ_HUMAN Decreases Methylation [20]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Activity [21]
Phytanoyl-CoA dioxygenase, peroxisomal (PHYH) OTUG4BWA PAHX_HUMAN Increases Expression [6]
Nuclear protein 1 (NUPR1) OT4FU8C0 NUPR1_HUMAN Increases Expression [6]
Alpha-1-antichymotrypsin (SERPINA3) OT9BP2S0 AACT_HUMAN Increases Expression [6]
Serine protease hepsin (HPN) OT7QNA61 HEPS_HUMAN Increases Expression [6]
Fatty acid-binding protein, liver (FABP1) OTR34ETM FABPL_HUMAN Increases Expression [6]
Asparagine synthetase (ASNS) OT8R922G ASNS_HUMAN Increases Expression [6]
Solute carrier family 2, facilitated glucose transporter member 3 (SLC2A3) OT2HZK5M GTR3_HUMAN Decreases Expression [6]
Lanosterol synthase (LSS) OT9W2SFH LSS_HUMAN Increases Expression [6]
Inhibin beta E chain (INHBE) OTOI2NYG INHBE_HUMAN Increases Expression [6]
Transgelin (TAGLN) OTAEZ0KP TAGL_HUMAN Decreases Expression [6]
Acid ceramidase (ASAH1) OT1DNGXL ASAH1_HUMAN Increases Expression [6]
Nuclear receptor subfamily 0 group B member 2 (NR0B2) OT7UVICX NR0B2_HUMAN Increases Expression [6]
Lysophospholipase D GDPD3 (GDPD3) OTOHM9QM GDPD3_HUMAN Increases Expression [6]
Fibronectin type III domain-containing protein 4 (FNDC4) OTOQK0WK FNDC4_HUMAN Increases Expression [6]
Protein DEPP1 (DEPP1) OTB36PHJ DEPP1_HUMAN Increases Expression [6]
Prostaglandin G/H synthase 2 (PTGS2) OT75U9M4 PGH2_HUMAN Decreases Expression [22]
Signal transducer and activator of transcription 3 (STAT3) OTAAGKYZ STAT3_HUMAN Decreases Expression [22]
Aromatase (CYP19A1) OTZ6XF74 CP19A_HUMAN Decreases Activity [23]
Mitogen-activated protein kinase kinase kinase 13 (MAP3K13) OTS93BTX M3K13_HUMAN Increases Expression [7]
Growth arrest and DNA damage-inducible protein GADD45 beta (GADD45B) OTL9I7LO GA45B_HUMAN Increases Expression [7]
Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1) OTY9R6FZ ERN1_HUMAN Increases Expression [7]
Protein phosphatase 1 regulatory subunit 15A (PPP1R15A) OTYG179K PR15A_HUMAN Increases Expression [7]
Dual specificity protein phosphatase 14 (DUSP14) OTGODFCR DUS14_HUMAN Increases Expression [7]
Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) OTBMJUOC M4K4_HUMAN Decreases Expression [7]
Epidermal growth factor receptor (EGFR) OTAPLO1S EGFR_HUMAN Increases Expression [7]
Protein c-Fos (FOS) OTJBUVWS FOS_HUMAN Increases Expression [7]
Myc proto-oncogene protein (MYC) OTPV5LUK MYC_HUMAN Increases Expression [7]
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Increases Expression [24]
Alpha-crystallin A chain (CRYAA) OTSN7JUR CRYAA_HUMAN Increases Expression [7]
Albumin (ALB) OTVMM513 ALBU_HUMAN Affects Binding [25]
Platelet basic protein (PPBP) OT1FHGQS CXCL7_HUMAN Decreases Expression [26]
Platelet factor 4 (PF4) OTEMJU68 PLF4_HUMAN Decreases Expression [8]
Eukaryotic translation initiation factor 2 subunit 1 (EIF2S1) OTM0GDTP IF2A_HUMAN Increases Phosphorylation [7]
Transcription factor Jun (JUN) OTCYBO6X JUN_HUMAN Increases Expression [7]
Transcription factor AP-2-alpha (TFAP2A) OTMYT3NK AP2A_HUMAN Increases Expression [27]
Monocyte differentiation antigen CD14 (CD14) OT83GJ47 CD14_HUMAN Decreases Expression [7]
Heat shock 70 kDa protein 1A (HSPA1A) OTKGIE76 HS71A_HUMAN Increases Expression [7]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [24]
Heat shock cognate 71 kDa protein (HSPA8) OTJI2RCI HSP7C_HUMAN Decreases Expression [7]
Cyclic AMP-dependent transcription factor ATF-2 (ATF2) OTNIZPEA ATF2_HUMAN Increases Expression [7]
P-selectin (SELP) OTWR90PK LYAM3_HUMAN Decreases Expression [26]
Platelet endothelial cell adhesion molecule (PECAM1) OTXOM4D9 PECA1_HUMAN Decreases Expression [8]
E-selectin (SELE) OT33RZWY LYAM2_HUMAN Decreases Expression [26]
Stathmin (STMN1) OTDJ4RV0 STMN1_HUMAN Decreases Expression [7]
Heat shock 70 kDa protein 6 (HSPA6) OTH4S7WB HSP76_HUMAN Increases Expression [7]
Transcription factor JunD (JUND) OTNKACJD JUND_HUMAN Increases Expression [7]
Cyclic AMP-dependent transcription factor ATF-4 (ATF4) OTRFV19J ATF4_HUMAN Increases Expression [7]
Nuclear factor NF-kappa-B p105 subunit (NFKB1) OTNRRD8I NFKB1_HUMAN Increases Expression [7]
Ribosomal protein S6 kinase beta-1 (RPS6KB1) OTAELNGX KS6B1_HUMAN Decreases Phosphorylation [9]
Growth arrest and DNA damage-inducible protein GADD45 alpha (GADD45A) OTDRV63V GA45A_HUMAN Increases Expression [7]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Increases Phosphorylation [24]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Increases Phosphorylation [24]
Dual specificity protein phosphatase 1 (DUSP1) OTN6BR75 DUS1_HUMAN Increases Expression [7]
DNA damage-inducible transcript 3 protein (DDIT3) OTI8YKKE DDIT3_HUMAN Increases Expression [7]
Mitogen-activated protein kinase kinase kinase 8 (MAP3K8) OTOZTA1F M3K8_HUMAN Increases Expression [7]
Serine/threonine-protein kinase mTOR (MTOR) OTHH8KU7 MTOR_HUMAN Decreases Phosphorylation [9]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [7]
Translocon-associated protein subunit beta (SSR2) OTQJSL7M SSRB_HUMAN Increases Expression [7]
Caspase-4 (CASP4) OTVQTV1L CASP4_HUMAN Increases Cleavage [7]
Ribosomal protein S6 kinase alpha-3 (RPS6KA3) OTYJNNMD KS6A3_HUMAN Decreases Expression [7]
Caspase-7 (CASP7) OTAPJ040 CASP7_HUMAN Increases Activity [7]
Protein transport protein Sec61 subunit gamma (SEC61G) OT7MJRXY SC61G_HUMAN Decreases Expression [7]
E3 ubiquitin-protein ligase RBX1 (RBX1) OTYA1UIO RBX1_HUMAN Decreases Expression [7]
S-phase kinase-associated protein 1 (SKP1) OT5BPAZ4 SKP1_HUMAN Decreases Expression [7]
Nuclear factor NF-kappa-B p100 subunit (NFKB2) OTS231V7 NFKB2_HUMAN Increases Expression [7]
Transcription factor RelB (RELB) OTU3QYEF RELB_HUMAN Increases Expression [7]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Decreases Expression [24]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [28]
Acetyl-CoA carboxylase 1 (ACACA) OT5CQPZY ACACA_HUMAN Increases Phosphorylation [9]
Dual specificity protein phosphatase 8 (DUSP8) OTPLMPG9 DUS8_HUMAN Increases Expression [7]
Sequestosome-1 (SQSTM1) OTGY5D5J SQSTM_HUMAN Increases Expression [9]
Cullin-1 (CUL1) OTXPE1UZ CUL1_HUMAN Decreases Expression [7]
Homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 1 protein (HERPUD1) OT9EROL6 HERP1_HUMAN Increases Expression [7]
Serine/threonine-protein kinase STK11 (STK11) OT1YZSP3 STK11_HUMAN Increases Phosphorylation [9]
Nuclear factor erythroid 2-related factor 2 (NFE2L2) OT0HENJ5 NF2L2_HUMAN Increases Expression [7]
E3 ubiquitin-protein ligase synoviolin (SYVN1) OTZ4ZJP5 SYVN1_HUMAN Increases Expression [7]
Dual specificity protein phosphatase 16 (DUSP16) OTK7S078 DUS16_HUMAN Increases Expression [7]
Microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B) OTUYHB84 MLP3B_HUMAN Increases Lipidation [9]
DnaJ homolog subfamily C member 5 (DNAJC5) OTCZDXAL DNJC5_HUMAN Increases Expression [29]
Eukaryotic translation initiation factor 2-alpha kinase 3 (EIF2AK3) OT0DZGY4 E2AK3_HUMAN Increases Expression [7]
Serine/threonine-protein kinase TAO2 (TAOK2) OTNUMOZ1 TAOK2_HUMAN Increases Expression [7]
C-Jun-amino-terminal kinase-interacting protein 3 (MAPK8IP3) OT0X8ACY JIP3_HUMAN Increases Expression [7]
Dual specificity protein phosphatase 10 (DUSP10) OTNG467B DUS10_HUMAN Increases Expression [7]
Sodium-dependent serotonin transporter (SLC6A4) OT6FGDLW SC6A4_HUMAN Increases Response To Substance [30]
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⏷ Show the Full List of 88 DOT(s)
Indication(s) of Venlafaxine
Disease Entry ICD 11 Status REF
Anxiety disorder 6B00-6B0Z Approved [4]
Depression 6A70-6A7Z Approved [5]
Major depressive disorder 6A70.3 Approved [4]
Panic disorder 6B01 Approved [4]
Venlafaxine Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Norepinephrine transporter (NET) TTAWNKZ SC6A2_HUMAN Inhibitor [31]
Serotonin transporter (SERT) TT3ROYC SC6A4_HUMAN Inhibitor [31]
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Venlafaxine Interacts with 4 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [32]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [33]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [34]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [34]
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Venlafaxine Interacts with 2 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 2D6 (CYP2D6) OTZJC802 CP2D6_HUMAN Increases ADR [35]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases ADR [36]
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References

1 ClinicalTrials.gov (NCT00043550) Treatments for Depression: Drug Versus Psychotherapy
2 Sertraline FDA Label
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: 4798).
4 Venlafaxine 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: 7321).
6 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.
7 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.
8 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.
9 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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28 Why are most phospholipidosis inducers also hERG blockers?. Arch Toxicol. 2017 Dec;91(12):3885-3895. doi: 10.1007/s00204-017-1995-9. Epub 2017 May 27.
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30 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.
31 Clinically relevant drug interactions with new generation antidepressants and antipsychotics. Ther Umsch. 2009 Jun;66(6):485-92.
32 Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
33 The associations between CYP2D6 metabolizer status and pharmacokinetics and clinical outcomes of venlafaxine: a systematic review and meta-analysis. Pharmacopsychiatry. 2019 Sep;52(5):222-231.
34 O- and N-demethylation of venlafaxine in vitro by human liver microsomes and by microsomes from cDNA-transfected cells: effect of metabolic inhibitors and SSRI antidepressants. Neuropsychopharmacology. 1999 May;20(5):480-90.
35 CYP2D6 polymorphism and clinical effect of the antidepressant venlafaxine. J Clin Pharm Ther. 2006 Oct;31(5):493-502.
36 ABCB1 gene variants influence tolerance to selective serotonin reuptake inhibitors in a large sample of Dutch cases with major depressive disorder. Pharmacogenomics J. 2013 Aug;13(4):349-53.