Details of the Drug Combination

General Information of Drug Combination (ID: DCEJ70F)

• Drug Combination Name: Imipramine + Fluoxetine
• Indication: Major Depression; Status: Phase 1 [1]
• Component Drugs:
  Imipramine (DM2NUH3): Small molecular drug
  Fluoxetine (DM3PD2C): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Imipramine

Disease Entry	ICD 11	Status	REF
Depression	6A70-6A7Z	Approved	[2]
Nocturia	MF55	Approved	[3]

Imipramine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Norepinephrine transporter (NET)	TTAWNKZ	SC6A2_HUMAN	Inhibitor	[9]

Imipramine 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]

Imipramine Interacts with 9 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]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[13]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[14]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[15]
Cytochrome P450 2C18 (CYP2C18)	DEZMWRE	CP2CI_HUMAN	Metabolism	[12]
Cytochrome P450 2B6 (CYP2B6)	DEPKLMQ	CP2B6_HUMAN	Metabolism	[12]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[16]
Docosahexaenoic acid omega-hydroxylase (CYP4F11)	DEIZLTN	CP4FB_HUMAN	Metabolism	[17]

Imipramine Interacts with 32 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Glutathione S-transferase P (GSTP1)	OTLP0A0Y	GSTP1_HUMAN	Decreases Activity	[18]
Nuclear protein 1 (NUPR1)	OT4FU8C0	NUPR1_HUMAN	Increases Expression	[7]
Alpha-1-antichymotrypsin (SERPINA3)	OT9BP2S0	AACT_HUMAN	Increases Expression	[7]
Serine protease hepsin (HPN)	OT7QNA61	HEPS_HUMAN	Increases Expression	[7]
Fatty acid-binding protein, liver (FABP1)	OTR34ETM	FABPL_HUMAN	Increases Expression	[7]
Asparagine synthetase (ASNS)	OT8R922G	ASNS_HUMAN	Increases Expression	[7]
Solute carrier family 2, facilitated glucose transporter member 3 (SLC2A3)	OT2HZK5M	GTR3_HUMAN	Decreases Expression	[7]
Lanosterol synthase (LSS)	OT9W2SFH	LSS_HUMAN	Increases Expression	[7]
Inhibin beta E chain (INHBE)	OTOI2NYG	INHBE_HUMAN	Increases Expression	[7]
Transgelin (TAGLN)	OTAEZ0KP	TAGL_HUMAN	Decreases Expression	[7]
Acid ceramidase (ASAH1)	OT1DNGXL	ASAH1_HUMAN	Increases Expression	[7]
Nuclear receptor subfamily 0 group B member 2 (NR0B2)	OT7UVICX	NR0B2_HUMAN	Increases Expression	[7]
Lysophospholipase D GDPD3 (GDPD3)	OTOHM9QM	GDPD3_HUMAN	Increases Expression	[7]
Fibronectin type III domain-containing protein 4 (FNDC4)	OTOQK0WK	FNDC4_HUMAN	Increases Expression	[7]
Protein DEPP1 (DEPP1)	OTB36PHJ	DEPP1_HUMAN	Increases Expression	[7]
Acetylcholinesterase (ACHE)	OT2H8HG6	ACES_HUMAN	Decreases Activity	[19]
Stearoyl-CoA desaturase (SCD)	OTB1073G	SCD_HUMAN	Increases Expression	[20]
Transmembrane protease serine 2 (TMPRSS2)	OTN44YQ5	TMPS2_HUMAN	Increases Expression	[21]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Affects Binding	[22]
Beta-2 adrenergic receptor (ADRB2)	OTSDOX4Q	ADRB2_HUMAN	Decreases Expression	[23]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[24]
Alpha-1-acid glycoprotein 2 (ORM2)	OTRJGZP8	A1AG2_HUMAN	Affects Binding	[25]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[26]
Caspase-7 (CASP7)	OTAPJ040	CASP7_HUMAN	Increases Activity	[26]
Heat shock factor protein 1 (HSF1)	OTYNJ4KP	HSF1_HUMAN	Decreases Activity	[27]
Hydroxymethylglutaryl-CoA synthase, cytoplasmic (HMGCS1)	OTCO26FV	HMCS1_HUMAN	Increases Expression	[20]
Glutamate receptor ionotropic, NMDA 1 (GRIN1)	OTZ5YBO8	NMDZ1_HUMAN	Decreases Expression	[28]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Decreases Activity	[29]
Multidrug and toxin extrusion protein 1 (SLC47A1)	OTZX0U5Q	S47A1_HUMAN	Decreases Activity	[30]
Angiotensin-converting enzyme 2 (ACE2)	OTTRZGU7	ACE2_HUMAN	Decreases Expression	[21]
DnaJ homolog subfamily C member 5 (DNAJC5)	OTCZDXAL	DNJC5_HUMAN	Increases Expression	[31]
SH3 and multiple ankyrin repeat domains protein 2 (SHANK2)	OTSQTPFQ	SHAN2_HUMAN	Decreases Expression	[28]

Indication(s) of Fluoxetine

Disease Entry	ICD 11	Status	REF
Bipolar depression	N.A.	Approved	[4]
Bulimia nervosa	6B81	Approved	[4]
Depression	6A70-6A7Z	Approved	[5]
Intracerebral hemorrhage	N.A.	Approved	[4]
Major depressive disorder	6A70.3	Approved	[4]
Obsessive compulsive disorder	6B20	Approved	[4]
Panic disorder	6B01	Approved	[4]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 3	[6]

Fluoxetine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Serotonin transporter (SERT)	TT3ROYC	SC6A4_HUMAN	Modulator	[34]

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	[35]

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	[36]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[37]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[38]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[38]
Cytochrome P450 2E1 (CYP2E1)	DEVDYN7	CP2E1_HUMAN	Metabolism	[39]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[40]
Cytochrome P450 2B6 (CYP2B6)	DEPKLMQ	CP2B6_HUMAN	Metabolism	[41]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[42]

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	[43]
Cytochrome P450 2C8 (CYP2C8)	OTHCWT42	CP2C8_HUMAN	Decreases Activity	[44]
Nuclear protein 1 (NUPR1)	OT4FU8C0	NUPR1_HUMAN	Increases Expression	[7]
Alpha-1-antichymotrypsin (SERPINA3)	OT9BP2S0	AACT_HUMAN	Increases Expression	[7]
Serine protease hepsin (HPN)	OT7QNA61	HEPS_HUMAN	Increases Expression	[7]
Fatty acid-binding protein, liver (FABP1)	OTR34ETM	FABPL_HUMAN	Increases Expression	[7]
Asparagine synthetase (ASNS)	OT8R922G	ASNS_HUMAN	Increases Expression	[7]
Solute carrier family 2, facilitated glucose transporter member 3 (SLC2A3)	OT2HZK5M	GTR3_HUMAN	Decreases Expression	[7]
Lanosterol synthase (LSS)	OT9W2SFH	LSS_HUMAN	Increases Expression	[7]
Inhibin beta E chain (INHBE)	OTOI2NYG	INHBE_HUMAN	Increases Expression	[7]
AP-1 complex subunit sigma-1A (AP1S1)	OTQ2H8DN	AP1S1_HUMAN	Decreases Expression	[7]
Transgelin (TAGLN)	OTAEZ0KP	TAGL_HUMAN	Decreases Expression	[7]
Acid ceramidase (ASAH1)	OT1DNGXL	ASAH1_HUMAN	Increases Expression	[7]
Nuclear receptor subfamily 0 group B member 2 (NR0B2)	OT7UVICX	NR0B2_HUMAN	Increases Expression	[7]
Fibronectin type III domain-containing protein 4 (FNDC4)	OTOQK0WK	FNDC4_HUMAN	Increases Expression	[7]
Protein DEPP1 (DEPP1)	OTB36PHJ	DEPP1_HUMAN	Increases Expression	[7]
Lysophospholipase D GDPD3 (GDPD3)	OTOHM9QM	GDPD3_HUMAN	Increases Expression	[45]
5-hydroxytryptamine receptor 2C (HTR2C)	OT6H8DE0	5HT2C_HUMAN	Affects Binding	[46]
Protein EVI2A (EVI2A)	OTR8RUXQ	EVI2A_HUMAN	Increases Expression	[32]
Inactive phospholipase C-like protein 1 (PLCL1)	OTJL2C79	PLCL1_HUMAN	Increases Expression	[32]
Cyclin-G2 (CCNG2)	OTII38K2	CCNG2_HUMAN	Increases Expression	[32]
Kelch-like protein 24 (KLHL24)	OTWZSX5C	KLH24_HUMAN	Increases Expression	[32]
Cystine/glutamate transporter (SLC7A11)	OTKJ6PXW	XCT_HUMAN	Increases Expression	[32]
Aromatase (CYP19A1)	OTZ6XF74	CP19A_HUMAN	Decreases Activity	[47]
Stearoyl-CoA desaturase (SCD)	OTB1073G	SCD_HUMAN	Increases Expression	[20]
Ras-related protein Rab-7L1 (RAB29)	OTDZT6LP	RAB7L_HUMAN	Increases Expression	[33]
Insulin-induced gene 1 protein (INSIG1)	OTZF5X1D	INSI1_HUMAN	Increases Expression	[33]
Long-chain-fatty-acid--CoA ligase 4 (ACSL4)	OTI71MUJ	ACSL4_HUMAN	Increases Expression	[33]
Lathosterol oxidase (SC5D)	OT41KMW4	SC5D_HUMAN	Increases Expression	[33]
Membrane protein BRI3 (BRI3)	OT1RWIH7	BRI3_HUMAN	Increases Expression	[33]
Phospholipid-transporting ATPase ABCA1 (ABCA1)	OT94G6BQ	ABCA1_HUMAN	Decreases Expression	[33]
Fatty acid CoA ligase Acsl3 (ACSL3)	OT3MWER1	ACSL3_HUMAN	Increases Expression	[33]
Acyl-CoA 6-desaturase (FADS2)	OTUX531P	FADS2_HUMAN	Increases Expression	[33]
Protein c-Fos (FOS)	OTJBUVWS	FOS_HUMAN	Decreases Expression	[48]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Decreases Phosphorylation	[48]
Prolactin (PRL)	OTWFQGX7	PRL_HUMAN	Increases Expression	[49]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Decreases Activity	[50]
3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR)	OTRT3F3U	HMDH_HUMAN	Increases Expression	[33]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Expression	[48]
Transcription factor Jun (JUN)	OTCYBO6X	JUN_HUMAN	Decreases Expression	[48]
Fatty acid-binding protein, heart (FABP3)	OT562DA1	FABPH_HUMAN	Increases Expression	[33]
Fructose-bisphosphate aldolase C (ALDOC)	OTEC13I5	ALDOC_HUMAN	Increases Expression	[33]
Sphingomyelin phosphodiesterase (SMPD1)	OTZSMA54	ASM_HUMAN	Decreases Activity	[51]
HLA class II histocompatibility antigen, DP alpha 1 chain (HLA-DPA1)	OT7OG7Y2	DPA1_HUMAN	Affects Expression	[52]
Transcobalamin-2 (TCN2)	OT41D0L3	TCO2_HUMAN	Increases Expression	[33]
Cyclin-A2 (CCNA2)	OTPHHYZJ	CCNA2_HUMAN	Decreases Expression	[53]
Potassium voltage-gated channel subfamily A member 3 (KCNA3)	OTXSP3AA	KCNA3_HUMAN	Decreases Activity	[54]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Decreases Expression	[48]
G1/S-specific cyclin-E1 (CCNE1)	OTLD7UID	CCNE1_HUMAN	Affects Expression	[53]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[48]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[48]
Glucose-6-phosphatase catalytic subunit 1 (G6PC1)	OTJ6FM9F	G6PC1_HUMAN	Decreases Expression	[55]
Squalene synthase (FDFT1)	OTGDISIT	FDFT_HUMAN	Increases Expression	[33]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[48]
Melanocyte protein PMEL (PMEL)	OTCDDHHM	PMEL_HUMAN	Increases Expression	[33]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[26]
Cyclin-dependent kinase inhibitor 1B (CDKN1B)	OTNY5LLZ	CDN1B_HUMAN	Affects Expression	[53]
Caspase-7 (CASP7)	OTAPJ040	CASP7_HUMAN	Increases Activity	[26]
3-keto-steroid reductase/17-beta-hydroxysteroid dehydrogenase 7 (HSD17B7)	OTV7VOV3	DHB7_HUMAN	Increases Expression	[33]
Cyclin-dependent kinases regulatory subunit 1 (CKS1B)	OTNUPLUJ	CKS1_HUMAN	Decreases Expression	[53]
Hydroxymethylglutaryl-CoA synthase, cytoplasmic (HMGCS1)	OTCO26FV	HMCS1_HUMAN	Increases Expression	[20]
Mevalonate kinase (MVK)	OTHJCUKT	KIME_HUMAN	Increases Expression	[33]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Decreases Activity	[56]
Isopentenyl-diphosphate Delta-isomerase 1 (IDI1)	OTGM06VJ	IDI1_HUMAN	Increases Expression	[33]
Beclin-1 (BECN1)	OT4X293M	BECN1_HUMAN	Increases Expression	[57]
Squalene monooxygenase (SQLE)	OT0GGRDO	ERG1_HUMAN	Increases Expression	[33]
Phosphatidate phosphatase LPIN1 (LPIN1)	OTQ75KF2	LPIN1_HUMAN	Increases Expression	[33]
3-beta-hydroxysteroid-Delta(8),Delta(7)-isomerase (EBP)	OTSMGKXQ	EBP_HUMAN	Increases Expression	[33]
Mitochondrial fission regulator 1 (MTFR1)	OTLB1VFT	MTFR1_HUMAN	Increases Expression	[33]
Delta(24)-sterol reductase (DHCR24)	OTP301JW	DHC24_HUMAN	Increases Expression	[33]
Sterol-4-alpha-carboxylate 3-dehydrogenase, decarboxylating (NSDHL)	OTK3EJFD	NSDHL_HUMAN	Increases Expression	[33]
Methylsterol monooxygenase 1 (MSMO1)	OTKV62RZ	MSMO1_HUMAN	Increases Expression	[33]
Hypoxia-inducible factor 1-alpha (HIF1A)	OTADSC03	HIF1A_HUMAN	Increases Expression	[33]
Cytochrome P450 1B1 (CYP1B1)	OTYXFLSD	CP1B1_HUMAN	Decreases Activity	[58]
LON peptidase N-terminal domain and RING finger protein 1 (LONRF1)	OT0S9MFX	LONF1_HUMAN	Increases Expression	[33]
Type 1 phosphatidylinositol 4,5-bisphosphate 4-phosphatase (PIP4P1)	OT991XS0	PP4P1_HUMAN	Increases Expression	[33]
Osteopetrosis-associated transmembrane protein 1 (OSTM1)	OTKNJDH7	OSTM1_HUMAN	Increases Expression	[33]
Polypeptide N-acetylgalactosaminyltransferase 11 (GALNT11)	OTANT9E6	GLT11_HUMAN	Increases Expression	[33]
RCC1 and BTB domain-containing protein 1 (RCBTB1)	OTAYELI8	RCBT1_HUMAN	Increases Expression	[33]
Folliculin (FLCN)	OTVM78XM	FLCN_HUMAN	Increases Expression	[33]
Folliculin-interacting protein 1 (FNIP1)	OTB1CC41	FNIP1_HUMAN	Increases Expression	[33]
ATP-binding cassette sub-family C member 2 (ABCC2)	OTJSIGV5	MRP2_HUMAN	Increases Expression	[33]
StAR-related lipid transfer protein 4 (STARD4)	OTPQ0BFY	STAR4_HUMAN	Increases Expression	[33]
Sodium-coupled neutral amino acid symporter 2 (SLC38A2)	OTALABSK	S38A2_HUMAN	Increases Expression	[33]
Ethanolamine-phosphate cytidylyltransferase (PCYT2)	OTT8TAEA	PCY2_HUMAN	Increases Expression	[33]
Sialidase-1 (NEU1)	OTH9BY8Y	NEUR1_HUMAN	Increases Expression	[33]
17-beta-hydroxysteroid dehydrogenase 14 (HSD17B14)	OT0ETO72	DHB14_HUMAN	Increases Expression	[33]
Ethanolaminephosphotransferase 1 (SELENOI)	OTX2A47A	EPT1_HUMAN	Increases Expression	[33]
Pantothenate kinase 3 (PANK3)	OT77CFJ6	PANK3_HUMAN	Increases Expression	[33]
Acetyl-coenzyme A synthetase, cytoplasmic (ACSS2)	OTB1FZJU	ACSA_HUMAN	Increases Expression	[33]
1-acylglycerol-3-phosphate O-acyltransferase PNPLA3 (PNPLA3)	OTR4990X	PLPL3_HUMAN	Increases Expression	[33]
Maspardin (SPG21)	OTMKJSYS	SPG21_HUMAN	Increases Expression	[33]
7-dehydrocholesterol reductase (DHCR7)	OTLILBUI	DHCR7_HUMAN	Increases Expression	[33]
Potassium voltage-gated channel subfamily D member 3 (KCND3)	OTRPIH7J	KCND3_HUMAN	Decreases Activity	[59]
Ergosterol biosynthetic protein 28 homolog (ERG28)	OT2KAOBA	ERG28_HUMAN	Increases Expression	[33]
5-hydroxytryptamine receptor 1A (HTR1A)	OT38K9MK	5HT1A_HUMAN	Increases Response To Substance	[60]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Response To Substance	[61]
Tryptophan 5-hydroxylase 2 (TPH2)	OTKL5S1B	TPH2_HUMAN	Affects Response To Substance	[62]
Brain-derived neurotrophic factor (BDNF)	OTLGH7EW	BDNF_HUMAN	Increases Response To Substance	[63]

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