Details of the Drug Combination

General Information of Drug Combination (ID: DCP2633)

• Drug Combination Name: Ibuprofen + Morphine
• Indication: Postoperative Pain; Status: Phase 1 [1]
• Component Drugs:
  Ibuprofen (DM8VCBE): Small molecular drug
  Morphine (DMRMS0L): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Ibuprofen

Disease Entry	ICD 11	Status	REF
Dysmenorrhea	GA34.3	Approved	[2]
Fever	MG26	Approved	[2]
Headache	8A80-8A84	Approved	[2]
Osteoarthritis	FA00-FA05	Approved	[2]
Pain	MG30-MG3Z	Approved	[3]
Patent ductus arteriosus	N.A.	Approved	[2]

Ibuprofen Interacts with 4 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
C-X-C chemokine receptor type 1 (CXCR1)	TTMWT8Z	CXCR1_HUMAN	Inhibitor	[11]
Interleukin-8 (IL8)	TTCTE1G	IL8_HUMAN	Inhibitor	[12]
C-X-C chemokine receptor type 2 (CXCR2)	TT30C9G	CXCR2_HUMAN	Inhibitor	[11]
Prostaglandin G/H synthase 2 (COX-2)	TTVKILB	PGH2_HUMAN	Inhibitor	[13]

Ibuprofen Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Monocarboxylate transporter 2 (SLC16A7)	DTLT3UG	MOT2_HUMAN	Substrate	[14]
Probable small intestine urate exporter (SLC17A4)	DTHE530	S17A4_HUMAN	Substrate	[15]

Ibuprofen Interacts with 9 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[16]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[17]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[18]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[18]
UDP-glucuronosyltransferase 2B7 (UGT2B7)	DEB3CV1	UD2B7_HUMAN	Metabolism	[19]
UDP-glucuronosyltransferase 1A3 (UGT1A3)	DEF2WXN	UD13_HUMAN	Metabolism	[19]
UDP-glucuronosyltransferase 1A9 (UGT1A9)	DE85D2P	UD19_HUMAN	Metabolism	[19]
Alpha-methylacyl-CoA racemase (AMACR)	DEGKWJB	AMACR_HUMAN	Metabolism	[20]
Acyl-CoA thioesterase 2 (ACOT2)	DEMEPVJ	ACOT2_HUMAN	Metabolism	[21]

Ibuprofen Interacts with 122 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Solute carrier family 22 member 1 (SLC22A1)	OT7817I4	S22A1_HUMAN	Decreases Activity	[22]
Solute carrier family 22 member 6 (SLC22A6)	OTKRCBVM	S22A6_HUMAN	Decreases Activity	[22]
Organic anion transporter 7 (SLC22A9)	OTO4BJCC	S22A9_HUMAN	Decreases Activity	[22]
Solute carrier family 22 member 11 (SLC22A11)	OTAJLNJZ	S22AB_HUMAN	Decreases Activity	[22]
Solute carrier family 22 member 7 (SLC22A7)	OTKTNH1W	S22A7_HUMAN	Decreases Activity	[22]
Diamine acetyltransferase 1 (SAT1)	OT52AU22	SAT1_HUMAN	Increases Expression	[23]
Annexin A9 (ANXA9)	OTKNYMU2	ANXA9_HUMAN	Decreases Expression	[24]
Metastasis-associated protein MTA2 (MTA2)	OTCCYIQJ	MTA2_HUMAN	Increases Expression	[24]
Integrin beta-like protein 1 (ITGBL1)	OTJDHE17	ITGBL_HUMAN	Affects Expression	[24]
Annexin A1 (ANXA1)	OT5OFDJC	ANXA1_HUMAN	Affects Expression	[24]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Increases Expression	[24]
Peptide YY (PYY)	OTXX6AF5	PYY_HUMAN	Decreases Expression	[24]
Collagen alpha-1(XI) chain (COL11A1)	OTB0DRMS	COBA1_HUMAN	Affects Expression	[24]
Annexin A3 (ANXA3)	OTDD8OI7	ANXA3_HUMAN	Affects Expression	[24]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Increases Expression	[24]
Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1)	OTPWI88U	CEAM1_HUMAN	Affects Expression	[24]
Phospholipase A2, membrane associated (PLA2G2A)	OT1NY7BF	PA2GA_HUMAN	Affects Expression	[24]
Fatty acid-binding protein, adipocyte (FABP4)	OT3DKFOU	FABP4_HUMAN	Decreases Expression	[24]
Myelin and lymphocyte protein (MAL)	OTBM30SW	MAL_HUMAN	Increases Expression	[24]
Cadherin-3 (CDH3)	OTKNLQU7	CADH3_HUMAN	Affects Expression	[24]
Protein PML (PML)	OT6SM2GD	PML_HUMAN	Affects Expression	[24]
Tumor necrosis factor receptor superfamily member 3 (LTBR)	OT2HVZGV	TNR3_HUMAN	Decreases Expression	[24]
Protein FosB (FOSB)	OTW6C05J	FOSB_HUMAN	Increases Expression	[24]
Insulinoma-associated protein 1 (INSM1)	OTG8RV8E	INSM1_HUMAN	Decreases Expression	[24]
Max dimerization protein 1 (MXD1)	OTS5CTHX	MAD1_HUMAN	Increases Expression	[24]
Desmocollin-1 (DSC1)	OTNII6GZ	DSC1_HUMAN	Affects Expression	[24]
Corneodesmosin (CDSN)	OTQW4HV6	CDSN_HUMAN	Affects Expression	[24]
Microtubule-associated protein RP/EB family member 2 (MAPRE2)	OTAE3MX4	MARE2_HUMAN	Affects Expression	[24]
Voltage-dependent calcium channel subunit alpha-2/delta-3 (CACNA2D3)	OTEH9HGE	CA2D3_HUMAN	Affects Expression	[24]
Secreted frizzled-related protein 3 (FRZB)	OTTO3DPY	SFRP3_HUMAN	Affects Expression	[24]
Hydroperoxide isomerase ALOXE3 (ALOXE3)	OT76J52A	LOXE3_HUMAN	Affects Expression	[24]
Transmembrane protease serine 4 (TMPRSS4)	OTCCGY2K	TMPS4_HUMAN	Affects Expression	[24]
A disintegrin and metalloproteinase with thrombospondin motifs 8 (ADAMTS8)	OT2KFY1S	ATS8_HUMAN	Increases Expression	[24]
Aldo-keto reductase family 1 member C3 (AKR1C3)	OTU2SXBA	AK1C3_HUMAN	Decreases Activity	[25]
Aldo-keto reductase family 1 member C2 (AKR1C2)	OTQ2XMO3	AK1C2_HUMAN	Decreases Activity	[25]
Aldo-keto reductase family 1 member C1 (AKR1C1)	OTQKR4CM	AK1C1_HUMAN	Decreases Activity	[25]
PDZ and LIM domain protein 1 (PDLIM1)	OT4EGCPG	PDLI1_HUMAN	Decreases Expression	[9]
Branched-chain-amino-acid aminotransferase, mitochondrial (BCAT2)	OT8L6EGI	BCAT2_HUMAN	Increases Expression	[9]
Monocarboxylate transporter 7 (SLC16A6)	OT7BIIZX	MOT7_HUMAN	Increases Expression	[9]
Insulin-induced gene 1 protein (INSIG1)	OTZF5X1D	INSI1_HUMAN	Increases Expression	[9]
Cochlin (COCH)	OTBEHD89	COCH_HUMAN	Decreases Expression	[9]
5'-AMP-activated protein kinase subunit beta-2 (PRKAB2)	OTLVN68B	AAKB2_HUMAN	Decreases Expression	[9]
NUAK family SNF1-like kinase 1 (NUAK1)	OTLLHJJQ	NUAK1_HUMAN	Decreases Expression	[9]
Protein phosphatase 1 regulatory subunit 15A (PPP1R15A)	OTYG179K	PR15A_HUMAN	Increases Expression	[9]
Ribosomal L1 domain-containing protein 1 (RSL1D1)	OT3CL4R3	RL1D1_HUMAN	Increases Expression	[9]
Solute carrier organic anion transporter family member 2B1 (SLCO2B1)	OTERJ4VQ	SO2B1_HUMAN	Decreases Expression	[9]
Tumor necrosis factor alpha-induced protein 8 (TNFAIP8)	OT1G9297	TFIP8_HUMAN	Decreases Expression	[9]
Beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,6-N-acetylglucosaminyltransferase 3 (GCNT3)	OTQ9ALTR	GCNT3_HUMAN	Increases Expression	[9]
Protein AMBP (AMBP)	OTLU8GU8	AMBP_HUMAN	Decreases Expression	[9]
Fructose-bisphosphate aldolase A (ALDOA)	OTWRFTIB	ALDOA_HUMAN	Increases Expression	[9]
Alpha-enolase (ENO1)	OTB1KWJS	ENOA_HUMAN	Increases Expression	[9]
Bifunctional glutamate/proline--tRNA ligase (EPRS1)	OTXK0FLB	SYEP_HUMAN	Increases Expression	[9]
Amino acid transporter heavy chain SLC3A2 (SLC3A2)	OTBR33M9	4F2_HUMAN	Increases Expression	[9]
Solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1)	OTA675TJ	GTR1_HUMAN	Increases Expression	[9]
Histone H1.2 (H1-2)	OT0AVI4M	H12_HUMAN	Decreases Expression	[9]
Cyclic AMP-dependent transcription factor ATF-4 (ATF4)	OTRFV19J	ATF4_HUMAN	Affects Activity	[9]
Transcription factor E3 (TFE3)	OTM99ZWH	TFE3_HUMAN	Increases Expression	[9]
Tumor necrosis factor receptor superfamily member 6 (FAS)	OTP9XG86	TNR6_HUMAN	Decreases Expression	[9]
DnaJ homolog subfamily B member 2 (DNAJB2)	OTZHPV5M	DNJB2_HUMAN	Increases Expression	[9]
Adenylate kinase 4, mitochondrial (AK4)	OTA0T02Q	KAD4_HUMAN	Decreases Expression	[9]
ETS domain-containing protein Elk-4 (ELK4)	OTVSSEOE	ELK4_HUMAN	Increases Expression	[9]
14-3-3 protein sigma (SFN)	OTLJCZ1U	1433S_HUMAN	Increases Expression	[9]
Long-chain-fatty-acid--CoA ligase 1 (ACSL1)	OTB06ESI	ACSL1_HUMAN	Increases Expression	[9]
Isoleucine--tRNA ligase, cytoplasmic (IARS1)	OT9WXH5N	SYIC_HUMAN	Increases Expression	[9]
Neutral amino acid transporter A (SLC1A4)	OTVODHAE	SATT_HUMAN	Increases Expression	[9]
Ataxin-1 (ATXN1)	OTQF0HNR	ATX1_HUMAN	Increases Expression	[9]
Serine/threonine-protein kinase SIK1 (SIK1)	OT6FCHME	SIK1_HUMAN	Increases Expression	[9]
Large neutral amino acids transporter small subunit 1 (SLC7A5)	OT2WPVXD	LAT1_HUMAN	Increases Expression	[9]
1,4-alpha-glucan-branching enzyme (GBE1)	OTK2N05B	GLGB_HUMAN	Increases Expression	[9]
kinase isozyme 4, mitochondrial (PDK4)	OTCMHMBZ	PDK4_HUMAN	Increases Expression	[9]
Dual specificity protein phosphatase 5 (DUSP5)	OTH96RA7	DUS5_HUMAN	Increases Expression	[9]
Laminin subunit alpha-3 (LAMA3)	OTFME7HT	LAMA3_HUMAN	Decreases Expression	[9]
Tumor protein D53 (TPD52L1)	OTSA6U0I	TPD53_HUMAN	Increases Expression	[9]
Glycerol-3-phosphate acyltransferase 3 (GPAT3)	OTJUGPK0	GPAT3_HUMAN	Increases Expression	[9]
RRP12-like protein (RRP12)	OTQQAEH4	RRP12_HUMAN	Increases Expression	[9]
Arginine/serine-rich coiled-coil protein 2 (RSRC2)	OTLE0KQM	RSRC2_HUMAN	Increases Expression	[9]
Probable ATP-dependent RNA helicase DHX37 (DHX37)	OTM1A5KP	DHX37_HUMAN	Increases Expression	[9]
(Lyso)-N-acylphosphatidylethanolamine lipase (ABHD4)	OTQK3M9X	ABHD4_HUMAN	Increases Expression	[9]
Pantothenate kinase 1 (PANK1)	OT2CZVRT	PANK1_HUMAN	Increases Expression	[9]
SH3 domain and tetratricopeptide repeat-containing protein 1 (SH3TC1)	OT0HYZIU	S3TC1_HUMAN	Increases Expression	[9]
Sortilin-related receptor (SORL1)	OTQ8FFNS	SORL_HUMAN	Decreases Expression	[9]
Tumor protein p53-inducible nuclear protein 1 (TP53INP1)	OT2363Z9	T53I1_HUMAN	Decreases Expression	[9]
Carboxymethylenebutenolidase homolog (CMBL)	OT8H3S3G	CMBL_HUMAN	Decreases Expression	[9]
Protein FAM89A (FAM89A)	OTNASAXT	FA89A_HUMAN	Increases Expression	[9]
Protein FAM210B, mitochondrial (FAM210B)	OT2QHEQ6	F210B_HUMAN	Decreases Expression	[9]
Spermatid perinuclear RNA-binding protein (STRBP)	OTU7XLZL	STRBP_HUMAN	Increases Expression	[9]
Perilipin-2 (PLIN2)	OTRXJ9UN	PLIN2_HUMAN	Increases Expression	[9]
ETS-related transcription factor Elf-4 (ELF4)	OT167PR5	ELF4_HUMAN	Increases Expression	[9]
Ferroptosis suppressor protein 1 (AIFM2)	OT57XWXO	FSP1_HUMAN	Increases Expression	[9]
Sulfiredoxin-1 (SRXN1)	OTYDBO4L	SRXN1_HUMAN	Increases Expression	[9]
Dual specificity protein phosphatase 22 (DUSP22)	OTEZ3U85	DUS22_HUMAN	Increases Expression	[9]
Phospholipase A and acyltransferase 2 (PLAAT2)	OTI5RMWB	PLAT2_HUMAN	Increases Expression	[9]
Leucine--tRNA ligase, cytoplasmic (LARS1)	OT4557NF	SYLC_HUMAN	Increases Expression	[9]
Mitochondrial fission process protein 1 (MTFP1)	OT3L6F7U	MTFP1_HUMAN	Increases Expression	[9]
Brefeldin A-inhibited guanine nucleotide-exchange protein 2 (ARFGEF2)	OTM3CQZT	BIG2_HUMAN	Increases Expression	[9]
Protein piccolo (PCLO)	OTXJZZ98	PCLO_HUMAN	Increases Expression	[9]
Inhibitor of nuclear factor kappa-B kinase subunit alpha (CHUK)	OTLF4ZB1	IKKA_HUMAN	Decreases Activity	[26]
Tumor necrosis factor receptor superfamily member 21 (TNFRSF21)	OT3EDGXO	TNR21_HUMAN	Decreases Expression	[27]
Interstitial collagenase (MMP1)	OTI4I2V1	MMP1_HUMAN	Increases Expression	[28]
Amyloid-beta precursor protein (APP)	OTKFD7R4	A4_HUMAN	Decreases Expression	[29]
Eukaryotic translation initiation factor 4E (EIF4E)	OTDAWNLA	IF4E_HUMAN	Increases Phosphorylation	[30]
L-lactate dehydrogenase B chain (LDHB)	OT9B1CT3	LDHB_HUMAN	Affects Expression	[31]
Tumor necrosis factor receptor superfamily member 16 (NGFR)	OTPKSM49	TNR16_HUMAN	Increases Expression	[32]
Stromelysin-1 (MMP3)	OTGBI74Z	MMP3_HUMAN	Increases Expression	[28]
Heat shock cognate 71 kDa protein (HSPA8)	OTJI2RCI	HSP7C_HUMAN	Affects Localization	[33]
15-hydroxyprostaglandin dehydrogenase (HPGD)	OTYZI6JB	PGDH_HUMAN	Increases Expression	[34]
Phosphoglycerate mutase 1 (PGAM1)	OTZ5DB06	PGAM1_HUMAN	Increases Expression	[31]
Peroxiredoxin-6 (PRDX6)	OTS8KC8A	PRDX6_HUMAN	Affects Expression	[31]
Peroxiredoxin-2 (PRDX2)	OTLWCY9T	PRDX2_HUMAN	Increases Expression	[31]
Triosephosphate isomerase (TPI1)	OT14KP4B	TPIS_HUMAN	Increases Expression	[31]
GTP-binding nuclear protein Ran (RAN)	OT2TER5M	RAN_HUMAN	Affects Expression	[31]
Peptidyl-prolyl cis-trans isomerase A (PPIA)	OTHJMWQQ	PPIA_HUMAN	Affects Expression	[31]
Heat shock factor protein 1 (HSF1)	OTYNJ4KP	HSF1_HUMAN	Increases Activity	[35]
POU domain, class 5, transcription factor 1 (POU5F1)	OTDHHN7O	PO5F1_HUMAN	Decreases Expression	[36]
Cytochrome P450 4A11 (CYP4A11)	OTPU5J0S	CP4AB_HUMAN	Decreases Activity	[37]
Plectin (PLEC)	OTU4XDEG	PLEC_HUMAN	Increases Expression	[31]
Receptor tyrosine-protein kinase erbB-4 (ERBB4)	OT9L6C41	ERBB4_HUMAN	Affects Cleavage	[38]
Methylcytosine dioxygenase TET1 (TET1)	OTZDHT1D	TET1_HUMAN	Increases Expression	[36]
ATP-dependent RNA helicase DDX1 (DDX1)	OT3U8FD0	DDX1_HUMAN	Affects Expression	[31]
Endothelial PAS domain-containing protein 1 (EPAS1)	OTRE3O8U	EPAS1_HUMAN	Decreases Expression	[10]
DNA (DNMT3A)	OTEJP0GH	DNM3A_HUMAN	Decreases Expression	[36]
Arylamine N-acetyltransferase 2 (NAT2)	OTBPDQOY	ARY2_HUMAN	Increases ADR	[39]

Indication(s) of Morphine

Disease Entry	ICD 11	Status	REF
Advanced cancer	2A00-2F9Z	Approved	[4]
Chronic pain	MG30	Approved	[5]
Pain	MG30-MG3Z	Approved	[4]
Diarrhea	ME05.1	Investigative	[4]

Morphine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Opioid receptor mu (MOP)	TTKWM86	OPRM_HUMAN	Modulator	[43]

Morphine Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[44]
Multidrug resistance-associated protein 3 (ABCC3)	DTQ3ZHF	MRP3_HUMAN	Substrate	[45]

Morphine Interacts with 6 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[46]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[47]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[48]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[49]
UDP-glucuronosyltransferase 2B7 (UGT2B7)	DEB3CV1	UD2B7_HUMAN	Metabolism	[50]
UDP-glucuronosyltransferase 1A3 (UGT1A3)	DEF2WXN	UD13_HUMAN	Metabolism	[51]

Morphine Interacts with 22 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Response	[52]
Mu-type opioid receptor (OPRM1)	OT16AAT8	OPRM_HUMAN	Increases Response	[52]
Bcl-2-like protein 11 (BCL2L11)	OTNQQWFJ	B2L11_HUMAN	Increases Expression	[53]
LIM homeobox transcription factor 1-beta (LMX1B)	OTM8145D	LMX1B_HUMAN	Increases Expression	[54]
Krueppel-like factor 7 (KLF7)	OTS3YVA0	KLF7_HUMAN	Increases Expression	[55]
Protein c-Fos (FOS)	OTJBUVWS	FOS_HUMAN	Increases Expression	[56]
C-reactive protein (CRP)	OT0RFT8F	CRP_HUMAN	Increases Expression	[57]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Increases Expression	[58]
C-C motif chemokine 5 (CCL5)	OTSCA5CK	CCL5_HUMAN	Decreases Expression	[59]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Increases Phosphorylation	[60]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Increases Phosphorylation	[60]
Kappa-type opioid receptor (OPRK1)	OTXCZF4L	OPRK_HUMAN	Increases Activity	[61]
C-C motif chemokine 8 (CCL8)	OTCTWYN8	CCL8_HUMAN	Increases Secretion	[58]
Cytochrome c (CYCS)	OTBFALJD	CYC_HUMAN	Increases Secretion	[53]
Transcription factor p65 (RELA)	OTUJP9CN	TF65_HUMAN	Increases Phosphorylation	[56]
Bcl-2 homologous antagonist/killer (BAK1)	OTDP6ILW	BAK_HUMAN	Increases Expression	[62]
DNA damage-binding protein 2 (DDB2)	OTO8HVVB	DDB2_HUMAN	Increases Expression	[54]
Ninjurin-1 (NINJ1)	OTLRZ1EU	NINJ1_HUMAN	Increases Expression	[54]
Bcl-2-binding component 3, isoforms 3/4 (BBC3)	OTUAXDAY	BBC3B_HUMAN	Increases Expression	[54]
Cocaine esterase (CES2)	OTC647SQ	EST2_HUMAN	Increases Chemical Synthesis	[63]
Transcription factor Jun (JUN)	OTCYBO6X	JUN_HUMAN	Increases ADR	[39]
Mitogen-activated protein kinase 8 (MAPK8)	OTEREYS5	MK08_HUMAN	Increases ADR	[39]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Trauma	DC26UBS	N. A.	Phase 1	[64]

References

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