Details of the Drug Combination

General Information of Drug Combination (ID: DC2JFQ5)

Drug Combination Name
Edivoxetine Fluoxetine
Indication
Disease Entry Status REF
Major Depressive Disorder Phase 1 [1]
Component Drugs Edivoxetine   DMFTTMK Fluoxetine   DM3PD2C
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 Edivoxetine
Disease Entry ICD 11 Status REF
Major depressive disorder 6A70.3 Phase 3 [2]
Pediatric attention deficit hyperactivity disorder 6A05 Phase 3 [2]
Indication(s) of Fluoxetine
Disease Entry ICD 11 Status REF
Bipolar depression N.A. Approved [3]
Bulimia nervosa 6B81 Approved [3]
Depression 6A70-6A7Z Approved [4]
Intracerebral hemorrhage N.A. Approved [3]
Major depressive disorder 6A70.3 Approved [3]
Obsessive compulsive disorder 6B20 Approved [3]
Panic disorder 6B01 Approved [3]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 3 [5]
Fluoxetine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Serotonin transporter (SERT) TT3ROYC SC6A4_HUMAN Modulator [9]
------------------------------------------------------------------------------------
Fluoxetine Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [10]
------------------------------------------------------------------------------------
Fluoxetine Interacts with 8 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [11]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [12]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [13]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [13]
Cytochrome P450 2E1 (CYP2E1) DEVDYN7 CP2E1_HUMAN Metabolism [14]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [15]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Metabolism [16]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [17]
------------------------------------------------------------------------------------
⏷ Show the Full List of 8 DME(s)
Fluoxetine Interacts with 99 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Sodium-dependent serotonin transporter (SLC6A4) OT6FGDLW SC6A4_HUMAN Decreases Response To Substance [18]
Cytochrome P450 2C8 (CYP2C8) OTHCWT42 CP2C8_HUMAN Decreases Activity [19]
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]
AP-1 complex subunit sigma-1A (AP1S1) OTQ2H8DN AP1S1_HUMAN Decreases 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]
Fibronectin type III domain-containing protein 4 (FNDC4) OTOQK0WK FNDC4_HUMAN Increases Expression [6]
Protein DEPP1 (DEPP1) OTB36PHJ DEPP1_HUMAN Increases Expression [6]
Lysophospholipase D GDPD3 (GDPD3) OTOHM9QM GDPD3_HUMAN Increases Expression [20]
5-hydroxytryptamine receptor 2C (HTR2C) OT6H8DE0 5HT2C_HUMAN Affects Binding [21]
Protein EVI2A (EVI2A) OTR8RUXQ EVI2A_HUMAN Increases Expression [7]
Inactive phospholipase C-like protein 1 (PLCL1) OTJL2C79 PLCL1_HUMAN Increases Expression [7]
Cyclin-G2 (CCNG2) OTII38K2 CCNG2_HUMAN Increases Expression [7]
Kelch-like protein 24 (KLHL24) OTWZSX5C KLH24_HUMAN Increases Expression [7]
Cystine/glutamate transporter (SLC7A11) OTKJ6PXW XCT_HUMAN Increases Expression [7]
Aromatase (CYP19A1) OTZ6XF74 CP19A_HUMAN Decreases Activity [22]
Stearoyl-CoA desaturase (SCD) OTB1073G SCD_HUMAN Increases Expression [23]
Ras-related protein Rab-7L1 (RAB29) OTDZT6LP RAB7L_HUMAN Increases Expression [8]
Insulin-induced gene 1 protein (INSIG1) OTZF5X1D INSI1_HUMAN Increases Expression [8]
Long-chain-fatty-acid--CoA ligase 4 (ACSL4) OTI71MUJ ACSL4_HUMAN Increases Expression [8]
Lathosterol oxidase (SC5D) OT41KMW4 SC5D_HUMAN Increases Expression [8]
Membrane protein BRI3 (BRI3) OT1RWIH7 BRI3_HUMAN Increases Expression [8]
Phospholipid-transporting ATPase ABCA1 (ABCA1) OT94G6BQ ABCA1_HUMAN Decreases Expression [8]
Fatty acid CoA ligase Acsl3 (ACSL3) OT3MWER1 ACSL3_HUMAN Increases Expression [8]
Acyl-CoA 6-desaturase (FADS2) OTUX531P FADS2_HUMAN Increases Expression [8]
Protein c-Fos (FOS) OTJBUVWS FOS_HUMAN Decreases Expression [24]
Myc proto-oncogene protein (MYC) OTPV5LUK MYC_HUMAN Decreases Phosphorylation [24]
Prolactin (PRL) OTWFQGX7 PRL_HUMAN Increases Expression [25]
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Decreases Activity [26]
3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) OTRT3F3U HMDH_HUMAN Increases Expression [8]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Expression [24]
Transcription factor Jun (JUN) OTCYBO6X JUN_HUMAN Decreases Expression [24]
Fatty acid-binding protein, heart (FABP3) OT562DA1 FABPH_HUMAN Increases Expression [8]
Fructose-bisphosphate aldolase C (ALDOC) OTEC13I5 ALDOC_HUMAN Increases Expression [8]
Sphingomyelin phosphodiesterase (SMPD1) OTZSMA54 ASM_HUMAN Decreases Activity [27]
HLA class II histocompatibility antigen, DP alpha 1 chain (HLA-DPA1) OT7OG7Y2 DPA1_HUMAN Affects Expression [28]
Transcobalamin-2 (TCN2) OT41D0L3 TCO2_HUMAN Increases Expression [8]
Cyclin-A2 (CCNA2) OTPHHYZJ CCNA2_HUMAN Decreases Expression [29]
Potassium voltage-gated channel subfamily A member 3 (KCNA3) OTXSP3AA KCNA3_HUMAN Decreases Activity [30]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Decreases Expression [24]
G1/S-specific cyclin-E1 (CCNE1) OTLD7UID CCNE1_HUMAN Affects Expression [29]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [24]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [24]
Glucose-6-phosphatase catalytic subunit 1 (G6PC1) OTJ6FM9F G6PC1_HUMAN Decreases Expression [31]
Squalene synthase (FDFT1) OTGDISIT FDFT_HUMAN Increases Expression [8]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [24]
Melanocyte protein PMEL (PMEL) OTCDDHHM PMEL_HUMAN Increases Expression [8]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [32]
Cyclin-dependent kinase inhibitor 1B (CDKN1B) OTNY5LLZ CDN1B_HUMAN Affects Expression [29]
Caspase-7 (CASP7) OTAPJ040 CASP7_HUMAN Increases Activity [32]
3-keto-steroid reductase/17-beta-hydroxysteroid dehydrogenase 7 (HSD17B7) OTV7VOV3 DHB7_HUMAN Increases Expression [8]
Cyclin-dependent kinases regulatory subunit 1 (CKS1B) OTNUPLUJ CKS1_HUMAN Decreases Expression [29]
Hydroxymethylglutaryl-CoA synthase, cytoplasmic (HMGCS1) OTCO26FV HMCS1_HUMAN Increases Expression [23]
Mevalonate kinase (MVK) OTHJCUKT KIME_HUMAN Increases Expression [8]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [33]
Isopentenyl-diphosphate Delta-isomerase 1 (IDI1) OTGM06VJ IDI1_HUMAN Increases Expression [8]
Beclin-1 (BECN1) OT4X293M BECN1_HUMAN Increases Expression [34]
Squalene monooxygenase (SQLE) OT0GGRDO ERG1_HUMAN Increases Expression [8]
Phosphatidate phosphatase LPIN1 (LPIN1) OTQ75KF2 LPIN1_HUMAN Increases Expression [8]
3-beta-hydroxysteroid-Delta(8),Delta(7)-isomerase (EBP) OTSMGKXQ EBP_HUMAN Increases Expression [8]
Mitochondrial fission regulator 1 (MTFR1) OTLB1VFT MTFR1_HUMAN Increases Expression [8]
Delta(24)-sterol reductase (DHCR24) OTP301JW DHC24_HUMAN Increases Expression [8]
Sterol-4-alpha-carboxylate 3-dehydrogenase, decarboxylating (NSDHL) OTK3EJFD NSDHL_HUMAN Increases Expression [8]
Methylsterol monooxygenase 1 (MSMO1) OTKV62RZ MSMO1_HUMAN Increases Expression [8]
Hypoxia-inducible factor 1-alpha (HIF1A) OTADSC03 HIF1A_HUMAN Increases Expression [8]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Decreases Activity [35]
LON peptidase N-terminal domain and RING finger protein 1 (LONRF1) OT0S9MFX LONF1_HUMAN Increases Expression [8]
Type 1 phosphatidylinositol 4,5-bisphosphate 4-phosphatase (PIP4P1) OT991XS0 PP4P1_HUMAN Increases Expression [8]
Osteopetrosis-associated transmembrane protein 1 (OSTM1) OTKNJDH7 OSTM1_HUMAN Increases Expression [8]
Polypeptide N-acetylgalactosaminyltransferase 11 (GALNT11) OTANT9E6 GLT11_HUMAN Increases Expression [8]
RCC1 and BTB domain-containing protein 1 (RCBTB1) OTAYELI8 RCBT1_HUMAN Increases Expression [8]
Folliculin (FLCN) OTVM78XM FLCN_HUMAN Increases Expression [8]
Folliculin-interacting protein 1 (FNIP1) OTB1CC41 FNIP1_HUMAN Increases Expression [8]
ATP-binding cassette sub-family C member 2 (ABCC2) OTJSIGV5 MRP2_HUMAN Increases Expression [8]
StAR-related lipid transfer protein 4 (STARD4) OTPQ0BFY STAR4_HUMAN Increases Expression [8]
Sodium-coupled neutral amino acid symporter 2 (SLC38A2) OTALABSK S38A2_HUMAN Increases Expression [8]
Ethanolamine-phosphate cytidylyltransferase (PCYT2) OTT8TAEA PCY2_HUMAN Increases Expression [8]
Sialidase-1 (NEU1) OTH9BY8Y NEUR1_HUMAN Increases Expression [8]
17-beta-hydroxysteroid dehydrogenase 14 (HSD17B14) OT0ETO72 DHB14_HUMAN Increases Expression [8]
Ethanolaminephosphotransferase 1 (SELENOI) OTX2A47A EPT1_HUMAN Increases Expression [8]
Pantothenate kinase 3 (PANK3) OT77CFJ6 PANK3_HUMAN Increases Expression [8]
Acetyl-coenzyme A synthetase, cytoplasmic (ACSS2) OTB1FZJU ACSA_HUMAN Increases Expression [8]
1-acylglycerol-3-phosphate O-acyltransferase PNPLA3 (PNPLA3) OTR4990X PLPL3_HUMAN Increases Expression [8]
Maspardin (SPG21) OTMKJSYS SPG21_HUMAN Increases Expression [8]
7-dehydrocholesterol reductase (DHCR7) OTLILBUI DHCR7_HUMAN Increases Expression [8]
Potassium voltage-gated channel subfamily D member 3 (KCND3) OTRPIH7J KCND3_HUMAN Decreases Activity [36]
Ergosterol biosynthetic protein 28 homolog (ERG28) OT2KAOBA ERG28_HUMAN Increases Expression [8]
5-hydroxytryptamine receptor 1A (HTR1A) OT38K9MK 5HT1A_HUMAN Increases Response To Substance [37]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Response To Substance [38]
Tryptophan 5-hydroxylase 2 (TPH2) OTKL5S1B TPH2_HUMAN Affects Response To Substance [39]
Brain-derived neurotrophic factor (BDNF) OTLGH7EW BDNF_HUMAN Increases Response To Substance [40]
------------------------------------------------------------------------------------
⏷ Show the Full List of 99 DOT(s)

References

1 ClinicalTrials.gov (NCT01243957) A Study to Measure if There is Any Difference in How the Body Breaks Down or Inactivates Either Fluoxetine or LY2216684 When Both of These Medicines Are Given Together.
2 ClinicalTrials.gov (NCT01370499) A Study of LY2216684 in Patients With Major Depression Disorder. U.S. National Institutes of Health.
3 Fluoxetine FDA Label
4 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: 203).
5 Fluoxetine to Reduce Intubation and Death After COVID19 Infection
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 Transcriptome-based functional classifiers for direct immunotoxicity. Arch Toxicol. 2014 Mar;88(3):673-89.
8 Screening autism-associated environmental factors in differentiating human neural progenitors with fractional factorial design-based transcriptomics. Sci Rep. 2023 Jun 29;13(1):10519. doi: 10.1038/s41598-023-37488-0.
9 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
10 Fluoxetine and reversal of multidrug resistance. Cancer Lett. 2006 Jun 18;237(2):180-7.
11 O-Dealkylation of fluoxetine in relation to CYP2C19 gene dose and involvement of CYP3A4 in human liver microsomes. J Pharmacol Exp Ther. 2002 Jan;300(1):105-11.
12 Clinically significant psychotropic drug-drug interactions in the primary care setting. Curr Psychiatry Rep. 2012 Aug;14(4):376-90.
13 (R)-, (S)-, and racemic fluoxetine N-demethylation by human cytochrome P450 enzymes. Drug Metab Dispos. 2000 Oct;28(10):1187-91.
14 Antidepressant drugs in the elderly--role of the cytochrome P450 2D6. World J Biol Psychiatry. 2003 Apr;4(2):74-80.
15 Binding of CYP2C9 with diverse drugs and its implications for metabolic mechanism. Med Chem. 2009 May;5(3):263-70.
16 Molecular characterization of CYP2B6 substrates. Curr Drug Metab. 2008 Jun;9(5):363-73.
17 Effects of CYP2C19 genotype and CYP2C9 on fluoxetine N-demethylation in human liver microsomes. Acta Pharmacol Sin. 2001 Jan;22(1):85-90.
18 Age-dependent antidepressant pharmacogenomics: polymorphisms of the serotonin transporter and G protein beta3 subunit as predictors of response to fluoxetine and nortriptyline. Int J Neuropsychopharmacol. 2003 Dec;6(4):339-46. doi: 10.1017/S1461145703003663.
19 Mechanism-based inactivation of human cytochrome P4502C8 by drugs in vitro. J Pharmacol Exp Ther. 2004 Dec;311(3):996-1007.
20 Determination of phospholipidosis potential based on gene expression analysis in HepG2 cells. Toxicol Sci. 2007 Mar;96(1):101-14.
21 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.
22 Effects of selective serotonin reuptake inhibitors on three sex steroids in two versions of the aromatase enzyme inhibition assay and in the H295R cell assay. Toxicol In Vitro. 2015 Oct;29(7):1729-35.
23 Antidepressant drugs activate SREBP and up-regulate cholesterol and fatty acid biosynthesis in human glial cells. Neurosci Lett. 2006 Mar 13;395(3):185-90. doi: 10.1016/j.neulet.2005.10.096. Epub 2005 Dec 1.
24 Fluoxetine inhibits the extracellular signal regulated kinase pathway and suppresses growth of cancer cells. Cancer Biol Ther. 2008 Oct;7(10):1685-93. doi: 10.4161/cbt.7.10.6664. Epub 2008 Oct 22.
25 Serum prolactin levels among outpatients with major depressive disorder during the acute phase of treatment with fluoxetine. J Clin Psychiatry. 2006 Jun;67(6):952-7. doi: 10.4088/jcp.v67n0612.
26 Anti-inflammatory properties of desipramine and fluoxetine. Respir Res. 2007 May 3;8(1):35. doi: 10.1186/1465-9921-8-35.
27 Acid sphingomyelinase-ceramide system mediates effects of antidepressant drugs. Nat Med. 2013 Jul;19(7):934-8. doi: 10.1038/nm.3214. Epub 2013 Jun 16.
28 Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis. Chem Res Toxicol. 2015 May 18;28(5):927-34. doi: 10.1021/tx5005248. Epub 2015 Apr 3.
29 Fluoxetine mediates G0/G1 arrest by inducing functional inhibition of cyclin dependent kinase subunit (CKS)1. Biochem Pharmacol. 2008 May 15;75(10):1924-34. doi: 10.1016/j.bcp.2008.02.013. Epub 2008 Feb 17.
30 A cell-based Rb(+)-flux assay of the Kv1.3 potassium channel. Assay Drug Dev Technol. 2007 Jun;5(3):373-80. doi: 10.1089/adt.2006.004.
31 Downregulation of glucose-6-phosphatase expression contributes to fluoxetine-induced hepatic steatosis. J Appl Toxicol. 2021 Aug;41(8):1232-1240. doi: 10.1002/jat.4109. Epub 2020 Nov 12.
32 Palmitate increases the susceptibility of cells to drug-induced toxicity: an in vitro method to identify drugs with potential contraindications in patients with metabolic disease. Toxicol Sci. 2012 Oct;129(2):346-62. doi: 10.1093/toxsci/kfs208. Epub 2012 Jun 14.
33 Drug-induced long QT syndrome: hERG K+ channel block and disruption of protein trafficking by fluoxetine and norfluoxetine. Br J Pharmacol. 2006 Nov;149(5):481-9. doi: 10.1038/sj.bjp.0706892. Epub 2006 Sep 11.
34 The antidepressants maprotiline and fluoxetine induce Type II autophagic cell death in drug-resistant Burkitt's lymphoma. Int J Cancer. 2011 Apr 1;128(7):1712-23. doi: 10.1002/ijc.25477. Epub 2010 May 25.
35 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.
36 Establishment of ion channel and ABC transporter assays in 3D-cultured ReNcell VM on a 384-pillar plate for neurotoxicity potential. Toxicol In Vitro. 2022 Aug;82:105375. doi: 10.1016/j.tiv.2022.105375. Epub 2022 May 10.
37 Response to fluoxetine and serotonin 1A receptor (C-1019G) polymorphism in Taiwan Chinese major depressive disorder. Pharmacogenomics J. 2006 Jan-Feb;6(1):27-33. doi: 10.1038/sj.tpj.6500340.
38 Lymphoma cells protected from apoptosis by dysregulated bcl-2 continue to bind annexin V in response to B-cell receptor engagement: a cautionary tale. Leuk Res. 2006 Jan;30(1):77-80. doi: 10.1016/j.leukres.2005.05.018. Epub 2005 Aug 1.
39 Effect of repeated treatment with fluoxetine on tryptophan hydroxylase-2 gene expression in the rat brainstem. Pharmacol Biochem Behav. 2006 Sep;85(1):220-7. doi: 10.1016/j.pbb.2006.08.004. Epub 2006 Sep 18.
40 Association of brain-derived neurotrophic factor genetic Val66Met polymorphism with severity of depression, efficacy of fluoxetine and its side effects in Chinese major depressive patients. Neuropsychobiology. 2010;61(2):71-8. doi: 10.1159/000265132. Epub 2009 Dec 12.