Details of the Drug Combination

General Information of Drug Combination (ID: DCQPY5H)

• Drug Combination Name: Ketamine + Fluoxetine
• Indication: Bipolar Disorder; Status: Phase 4 [1]
• Component Drugs:
  Ketamine (DMT5HA4): Small molecular drug
  Fluoxetine (DM3PD2C): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Ketamine

Disease Entry	ICD 11	Status	REF
Anaesthesia	9A78.6	Approved	[2]
Anxiety	N.A.	Approved	[3]
Bipolar disorder	6A60	Approved	[3]
Depression	6A70-6A7Z	Approved	[3]
Traumatic brain injury	NA07.Z	Approved	[3]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2	[4]
Chronic pain	MG30	Investigative	[3]

Ketamine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
N-methyl-D-aspartate receptor (NMDAR)	TT9IK2Z	NOUNIPROTAC	Antagonist	[9]

Ketamine Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[10]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[10]
Cytochrome P450 2B6 (CYP2B6)	DEPKLMQ	CP2B6_HUMAN	Metabolism	[10]

Ketamine Interacts with 27 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Decreases Expression	[11]
Zinc finger protein SNAI2 (SNAI2)	OT7Y8EJ2	SNAI2_HUMAN	Increases Expression	[8]
Zinc finger protein SNAI1 (SNAI1)	OTDPYAMC	SNAI1_HUMAN	Increases Expression	[8]
Renin (REN)	OT52GZR2	RENI_HUMAN	Increases Expression	[12]
Angiotensinogen (AGT)	OTBZLYR3	ANGT_HUMAN	Decreases Expression	[12]
Transforming growth factor beta-1 proprotein (TGFB1)	OTV5XHVH	TGFB1_HUMAN	Increases Expression	[8]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Increases Secretion	[13]
Fibronectin (FN1)	OTB5ZN4Q	FINC_HUMAN	Increases Expression	[8]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Expression	[14]
Amyloid-beta precursor protein (APP)	OTKFD7R4	A4_HUMAN	Increases Expression	[15]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[16]
Endoplasmic reticulum chaperone BiP (HSPA5)	OTFUIRAO	BIP_HUMAN	Increases Expression	[16]
Cadherin-1 (CDH1)	OTFJMXPM	CADH1_HUMAN	Decreases Expression	[8]
Protein S100-A4 (S100A4)	OTLRGFSQ	S10A4_HUMAN	Increases Expression	[8]
DNA damage-inducible transcript 3 protein (DDIT3)	OTI8YKKE	DDIT3_HUMAN	Increases Expression	[16]
TGF-beta receptor type-1 (TGFBR1)	OT40S1SJ	TGFR1_HUMAN	Increases Expression	[8]
TGF-beta receptor type-2 (TGFBR2)	OT3P7GZP	TGFR2_HUMAN	Increases Expression	[8]
Leptin (LEP)	OT5Q7ODW	LEP_HUMAN	Decreases Expression	[16]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[17]
Proliferation marker protein Ki-67 (MKI67)	OTA8N1QI	KI67_HUMAN	Increases Expression	[14]
Leptin receptor (LEPR)	OT9H7G0C	LEPR_HUMAN	Decreases Expression	[16]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Activity	[17]
Caspase-6 (CASP6)	OTXLD3EC	CASP6_HUMAN	Increases Activity	[17]
Actin, aortic smooth muscle (ACTA2)	OTEDLG8E	ACTA_HUMAN	Increases Expression	[8]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Affects Localization	[17]
Sodium/hydrogen exchanger 6 (SLC9A6)	OT5N47TC	SL9A6_HUMAN	Decreases Expression	[15]
Apolipoprotein E (APOE)	OTFOWL2H	APOE_HUMAN	Decreases Response To Substance	[18]

Indication(s) of Fluoxetine

Disease Entry	ICD 11	Status	REF
Bipolar depression	N.A.	Approved	[5]
Bulimia nervosa	6B81	Approved	[5]
Depression	6A70-6A7Z	Approved	[6]
Intracerebral hemorrhage	N.A.	Approved	[5]
Major depressive disorder	6A70.3	Approved	[5]
Obsessive compulsive disorder	6B20	Approved	[5]
Panic disorder	6B01	Approved	[5]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 3	[7]

Fluoxetine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Serotonin transporter (SERT)	TT3ROYC	SC6A4_HUMAN	Modulator	[22]

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	[23]

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	[24]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[25]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[26]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[26]
Cytochrome P450 2E1 (CYP2E1)	DEVDYN7	CP2E1_HUMAN	Metabolism	[27]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[28]
Cytochrome P450 2B6 (CYP2B6)	DEPKLMQ	CP2B6_HUMAN	Metabolism	[29]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[30]

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	[31]
Cytochrome P450 2C8 (CYP2C8)	OTHCWT42	CP2C8_HUMAN	Decreases Activity	[32]
Nuclear protein 1 (NUPR1)	OT4FU8C0	NUPR1_HUMAN	Increases Expression	[19]
Alpha-1-antichymotrypsin (SERPINA3)	OT9BP2S0	AACT_HUMAN	Increases Expression	[19]
Serine protease hepsin (HPN)	OT7QNA61	HEPS_HUMAN	Increases Expression	[19]
Fatty acid-binding protein, liver (FABP1)	OTR34ETM	FABPL_HUMAN	Increases Expression	[19]
Asparagine synthetase (ASNS)	OT8R922G	ASNS_HUMAN	Increases Expression	[19]
Solute carrier family 2, facilitated glucose transporter member 3 (SLC2A3)	OT2HZK5M	GTR3_HUMAN	Decreases Expression	[19]
Lanosterol synthase (LSS)	OT9W2SFH	LSS_HUMAN	Increases Expression	[19]
Inhibin beta E chain (INHBE)	OTOI2NYG	INHBE_HUMAN	Increases Expression	[19]
AP-1 complex subunit sigma-1A (AP1S1)	OTQ2H8DN	AP1S1_HUMAN	Decreases Expression	[19]
Transgelin (TAGLN)	OTAEZ0KP	TAGL_HUMAN	Decreases Expression	[19]
Acid ceramidase (ASAH1)	OT1DNGXL	ASAH1_HUMAN	Increases Expression	[19]
Nuclear receptor subfamily 0 group B member 2 (NR0B2)	OT7UVICX	NR0B2_HUMAN	Increases Expression	[19]
Fibronectin type III domain-containing protein 4 (FNDC4)	OTOQK0WK	FNDC4_HUMAN	Increases Expression	[19]
Protein DEPP1 (DEPP1)	OTB36PHJ	DEPP1_HUMAN	Increases Expression	[19]
Lysophospholipase D GDPD3 (GDPD3)	OTOHM9QM	GDPD3_HUMAN	Increases Expression	[33]
5-hydroxytryptamine receptor 2C (HTR2C)	OT6H8DE0	5HT2C_HUMAN	Affects Binding	[34]
Protein EVI2A (EVI2A)	OTR8RUXQ	EVI2A_HUMAN	Increases Expression	[20]
Inactive phospholipase C-like protein 1 (PLCL1)	OTJL2C79	PLCL1_HUMAN	Increases Expression	[20]
Cyclin-G2 (CCNG2)	OTII38K2	CCNG2_HUMAN	Increases Expression	[20]
Kelch-like protein 24 (KLHL24)	OTWZSX5C	KLH24_HUMAN	Increases Expression	[20]
Cystine/glutamate transporter (SLC7A11)	OTKJ6PXW	XCT_HUMAN	Increases Expression	[20]
Aromatase (CYP19A1)	OTZ6XF74	CP19A_HUMAN	Decreases Activity	[35]
Stearoyl-CoA desaturase (SCD)	OTB1073G	SCD_HUMAN	Increases Expression	[36]
Ras-related protein Rab-7L1 (RAB29)	OTDZT6LP	RAB7L_HUMAN	Increases Expression	[21]
Insulin-induced gene 1 protein (INSIG1)	OTZF5X1D	INSI1_HUMAN	Increases Expression	[21]
Long-chain-fatty-acid--CoA ligase 4 (ACSL4)	OTI71MUJ	ACSL4_HUMAN	Increases Expression	[21]
Lathosterol oxidase (SC5D)	OT41KMW4	SC5D_HUMAN	Increases Expression	[21]
Membrane protein BRI3 (BRI3)	OT1RWIH7	BRI3_HUMAN	Increases Expression	[21]
Phospholipid-transporting ATPase ABCA1 (ABCA1)	OT94G6BQ	ABCA1_HUMAN	Decreases Expression	[21]
Fatty acid CoA ligase Acsl3 (ACSL3)	OT3MWER1	ACSL3_HUMAN	Increases Expression	[21]
Acyl-CoA 6-desaturase (FADS2)	OTUX531P	FADS2_HUMAN	Increases Expression	[21]
Protein c-Fos (FOS)	OTJBUVWS	FOS_HUMAN	Decreases Expression	[37]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Decreases Phosphorylation	[37]
Prolactin (PRL)	OTWFQGX7	PRL_HUMAN	Increases Expression	[38]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Decreases Activity	[39]
3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR)	OTRT3F3U	HMDH_HUMAN	Increases Expression	[21]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Expression	[37]
Transcription factor Jun (JUN)	OTCYBO6X	JUN_HUMAN	Decreases Expression	[37]
Fatty acid-binding protein, heart (FABP3)	OT562DA1	FABPH_HUMAN	Increases Expression	[21]
Fructose-bisphosphate aldolase C (ALDOC)	OTEC13I5	ALDOC_HUMAN	Increases Expression	[21]
Sphingomyelin phosphodiesterase (SMPD1)	OTZSMA54	ASM_HUMAN	Decreases Activity	[40]
HLA class II histocompatibility antigen, DP alpha 1 chain (HLA-DPA1)	OT7OG7Y2	DPA1_HUMAN	Affects Expression	[41]
Transcobalamin-2 (TCN2)	OT41D0L3	TCO2_HUMAN	Increases Expression	[21]
Cyclin-A2 (CCNA2)	OTPHHYZJ	CCNA2_HUMAN	Decreases Expression	[42]
Potassium voltage-gated channel subfamily A member 3 (KCNA3)	OTXSP3AA	KCNA3_HUMAN	Decreases Activity	[43]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Decreases Expression	[37]
G1/S-specific cyclin-E1 (CCNE1)	OTLD7UID	CCNE1_HUMAN	Affects Expression	[42]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[37]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[37]
Glucose-6-phosphatase catalytic subunit 1 (G6PC1)	OTJ6FM9F	G6PC1_HUMAN	Decreases Expression	[44]
Squalene synthase (FDFT1)	OTGDISIT	FDFT_HUMAN	Increases Expression	[21]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[37]
Melanocyte protein PMEL (PMEL)	OTCDDHHM	PMEL_HUMAN	Increases Expression	[21]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[45]
Cyclin-dependent kinase inhibitor 1B (CDKN1B)	OTNY5LLZ	CDN1B_HUMAN	Affects Expression	[42]
Caspase-7 (CASP7)	OTAPJ040	CASP7_HUMAN	Increases Activity	[45]
3-keto-steroid reductase/17-beta-hydroxysteroid dehydrogenase 7 (HSD17B7)	OTV7VOV3	DHB7_HUMAN	Increases Expression	[21]
Cyclin-dependent kinases regulatory subunit 1 (CKS1B)	OTNUPLUJ	CKS1_HUMAN	Decreases Expression	[42]
Hydroxymethylglutaryl-CoA synthase, cytoplasmic (HMGCS1)	OTCO26FV	HMCS1_HUMAN	Increases Expression	[36]
Mevalonate kinase (MVK)	OTHJCUKT	KIME_HUMAN	Increases Expression	[21]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Decreases Activity	[46]
Isopentenyl-diphosphate Delta-isomerase 1 (IDI1)	OTGM06VJ	IDI1_HUMAN	Increases Expression	[21]
Beclin-1 (BECN1)	OT4X293M	BECN1_HUMAN	Increases Expression	[47]
Squalene monooxygenase (SQLE)	OT0GGRDO	ERG1_HUMAN	Increases Expression	[21]
Phosphatidate phosphatase LPIN1 (LPIN1)	OTQ75KF2	LPIN1_HUMAN	Increases Expression	[21]
3-beta-hydroxysteroid-Delta(8),Delta(7)-isomerase (EBP)	OTSMGKXQ	EBP_HUMAN	Increases Expression	[21]
Mitochondrial fission regulator 1 (MTFR1)	OTLB1VFT	MTFR1_HUMAN	Increases Expression	[21]
Delta(24)-sterol reductase (DHCR24)	OTP301JW	DHC24_HUMAN	Increases Expression	[21]
Sterol-4-alpha-carboxylate 3-dehydrogenase, decarboxylating (NSDHL)	OTK3EJFD	NSDHL_HUMAN	Increases Expression	[21]
Methylsterol monooxygenase 1 (MSMO1)	OTKV62RZ	MSMO1_HUMAN	Increases Expression	[21]
Hypoxia-inducible factor 1-alpha (HIF1A)	OTADSC03	HIF1A_HUMAN	Increases Expression	[21]
Cytochrome P450 1B1 (CYP1B1)	OTYXFLSD	CP1B1_HUMAN	Decreases Activity	[48]
LON peptidase N-terminal domain and RING finger protein 1 (LONRF1)	OT0S9MFX	LONF1_HUMAN	Increases Expression	[21]
Type 1 phosphatidylinositol 4,5-bisphosphate 4-phosphatase (PIP4P1)	OT991XS0	PP4P1_HUMAN	Increases Expression	[21]
Osteopetrosis-associated transmembrane protein 1 (OSTM1)	OTKNJDH7	OSTM1_HUMAN	Increases Expression	[21]
Polypeptide N-acetylgalactosaminyltransferase 11 (GALNT11)	OTANT9E6	GLT11_HUMAN	Increases Expression	[21]
RCC1 and BTB domain-containing protein 1 (RCBTB1)	OTAYELI8	RCBT1_HUMAN	Increases Expression	[21]
Folliculin (FLCN)	OTVM78XM	FLCN_HUMAN	Increases Expression	[21]
Folliculin-interacting protein 1 (FNIP1)	OTB1CC41	FNIP1_HUMAN	Increases Expression	[21]
ATP-binding cassette sub-family C member 2 (ABCC2)	OTJSIGV5	MRP2_HUMAN	Increases Expression	[21]
StAR-related lipid transfer protein 4 (STARD4)	OTPQ0BFY	STAR4_HUMAN	Increases Expression	[21]
Sodium-coupled neutral amino acid symporter 2 (SLC38A2)	OTALABSK	S38A2_HUMAN	Increases Expression	[21]
Ethanolamine-phosphate cytidylyltransferase (PCYT2)	OTT8TAEA	PCY2_HUMAN	Increases Expression	[21]
Sialidase-1 (NEU1)	OTH9BY8Y	NEUR1_HUMAN	Increases Expression	[21]
17-beta-hydroxysteroid dehydrogenase 14 (HSD17B14)	OT0ETO72	DHB14_HUMAN	Increases Expression	[21]
Ethanolaminephosphotransferase 1 (SELENOI)	OTX2A47A	EPT1_HUMAN	Increases Expression	[21]
Pantothenate kinase 3 (PANK3)	OT77CFJ6	PANK3_HUMAN	Increases Expression	[21]
Acetyl-coenzyme A synthetase, cytoplasmic (ACSS2)	OTB1FZJU	ACSA_HUMAN	Increases Expression	[21]
1-acylglycerol-3-phosphate O-acyltransferase PNPLA3 (PNPLA3)	OTR4990X	PLPL3_HUMAN	Increases Expression	[21]
Maspardin (SPG21)	OTMKJSYS	SPG21_HUMAN	Increases Expression	[21]
7-dehydrocholesterol reductase (DHCR7)	OTLILBUI	DHCR7_HUMAN	Increases Expression	[21]
Potassium voltage-gated channel subfamily D member 3 (KCND3)	OTRPIH7J	KCND3_HUMAN	Decreases Activity	[49]
Ergosterol biosynthetic protein 28 homolog (ERG28)	OT2KAOBA	ERG28_HUMAN	Increases Expression	[21]
5-hydroxytryptamine receptor 1A (HTR1A)	OT38K9MK	5HT1A_HUMAN	Increases Response To Substance	[50]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Response To Substance	[51]
Tryptophan 5-hydroxylase 2 (TPH2)	OTKL5S1B	TPH2_HUMAN	Affects Response To Substance	[52]
Brain-derived neurotrophic factor (BDNF)	OTLGH7EW	BDNF_HUMAN	Increases Response To Substance	[53]

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