Details of the Drug Combination

General Information of Drug Combination (ID: DCDIPAY)

• Drug Combination Name: Hydromorphone + Morphine
• Indication: Pain, Postoperative; Status: Phase 1 [1]
• Component Drugs:
  Hydromorphone (DMHP21E): Small molecular drug
  Morphine (DMRMS0L): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Hydromorphone

Disease Entry	ICD 11	Status	REF
Back pain	ME84.Z	Approved	[2]
Common cold	CA00	Approved	[2]
Cough	MD12	Approved	[2]
Pain	MG30-MG3Z	Approved	[3]
Chronic pain	MG30	Phase 3	[4]

Hydromorphone Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Opioid receptor mu (MOP)	TTKWM86	OPRM_HUMAN	Inhibitor	[6]
Opioid receptor delta (OPRD1)	TT27RFC	OPRD_HUMAN	Binder	[7]

Hydromorphone Interacts with 6 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[8]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[9]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[10]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[11]
UDP-glucuronosyltransferase 2B7 (UGT2B7)	DEB3CV1	UD2B7_HUMAN	Metabolism	[12]
UDP-glucuronosyltransferase 1A3 (UGT1A3)	DEF2WXN	UD13_HUMAN	Metabolism	[12]

Hydromorphone Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
5-hydroxytryptamine receptor 3A (HTR3A)	OTAIV1AK	5HT3A_HUMAN	Affects Activity	[13]

Indication(s) of Morphine

Disease Entry	ICD 11	Status	REF
Advanced cancer	2A00-2F9Z	Approved	[5]
Chronic pain	MG30	Approved	[3]
Pain	MG30-MG3Z	Approved	[5]
Diarrhea	ME05.1	Investigative	[5]

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	[17]

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	[18]
Multidrug resistance-associated protein 3 (ABCC3)	DTQ3ZHF	MRP3_HUMAN	Substrate	[19]

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	[20]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[21]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[22]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[23]
UDP-glucuronosyltransferase 2B7 (UGT2B7)	DEB3CV1	UD2B7_HUMAN	Metabolism	[24]
UDP-glucuronosyltransferase 1A3 (UGT1A3)	DEF2WXN	UD13_HUMAN	Metabolism	[25]

Morphine Interacts with 47 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2D6 (CYP2D6)	OTZJC802	CP2D6_HUMAN	Affects Chemical Synthesis	[26]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Response	[27]
Mu-type opioid receptor (OPRM1)	OT16AAT8	OPRM_HUMAN	Increases Response	[27]
Toll-like receptor 4 (TLR4)	OTP7ML3S	TLR4_HUMAN	Affects Binding	[28]
Bcl-2-like protein 11 (BCL2L11)	OTNQQWFJ	B2L11_HUMAN	Increases Expression	[29]
LIM homeobox transcription factor 1-beta (LMX1B)	OTM8145D	LMX1B_HUMAN	Increases Expression	[30]
Krueppel-like factor 7 (KLF7)	OTS3YVA0	KLF7_HUMAN	Increases Expression	[31]
Protein c-Fos (FOS)	OTJBUVWS	FOS_HUMAN	Increases Expression	[32]
C-reactive protein (CRP)	OT0RFT8F	CRP_HUMAN	Increases Expression	[33]
Apolipoprotein B-100 (APOB)	OTH0UOCZ	APOB_HUMAN	Increases Expression	[33]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Increases Expression	[34]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Expression	[30]
Interleukin-4 (IL4)	OTOXBWAU	IL4_HUMAN	Increases Expression	[35]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Increases Secretion	[34]
Coagulation factor VII (F7)	OTGNJ97M	FA7_HUMAN	Increases Expression	[33]
Fibroblast growth factor 2 (FGF2)	OT7YUJ9F	FGF2_HUMAN	Decreases Secretion	[34]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[36]
C-C motif chemokine 5 (CCL5)	OTSCA5CK	CCL5_HUMAN	Decreases Expression	[37]
NF-kappa-B inhibitor alpha (NFKBIA)	OTFT924M	IKBA_HUMAN	Increases Expression	[32]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Increases Phosphorylation	[35]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Increases Phosphorylation	[35]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Decreases Expression	[38]
Kappa-type opioid receptor (OPRK1)	OTXCZF4L	OPRK_HUMAN	Increases Activity	[39]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[36]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Activity	[29]
Interleukin-2 (IL2)	OTGI4NSA	IL2_HUMAN	Decreases Expression	[35]
Eukaryotic translation initiation factor 5A-1 (EIF5A)	OTQ8DJX5	IF5A1_HUMAN	Increases Expression	[30]
C-C motif chemokine 8 (CCL8)	OTCTWYN8	CCL8_HUMAN	Increases Secretion	[34]
Cytochrome c (CYCS)	OTBFALJD	CYC_HUMAN	Increases Secretion	[29]
Transcription factor p65 (RELA)	OTUJP9CN	TF65_HUMAN	Increases Phosphorylation	[32]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[36]
Beclin-1 (BECN1)	OT4X293M	BECN1_HUMAN	Increases Expression	[40]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Decreases Expression	[38]
Bcl-2 homologous antagonist/killer (BAK1)	OTDP6ILW	BAK_HUMAN	Increases Expression	[41]
DNA damage-binding protein 2 (DDB2)	OTO8HVVB	DDB2_HUMAN	Increases Expression	[30]
Ninjurin-1 (NINJ1)	OTLRZ1EU	NINJ1_HUMAN	Increases Expression	[30]
Bcl-2-binding component 3, isoforms 3/4 (BBC3)	OTUAXDAY	BBC3B_HUMAN	Increases Expression	[30]
Acetylcholinesterase (ACHE)	OT2H8HG6	ACES_HUMAN	Increases Chemical Synthesis	[42]
Interleukin-1 receptor antagonist protein (IL1RN)	OT308CBE	IL1RA_HUMAN	Affects Response To Substance	[43]
Protein kinase C alpha type (PRKCA)	OT5UWNRD	KPCA_HUMAN	Increases ADR	[44]
Beta-arrestin-2 (ARRB2)	OTAEJZCI	ARRB2_HUMAN	Affects Response To Substance	[45]
Cocaine esterase (CES2)	OTC647SQ	EST2_HUMAN	Increases Chemical Synthesis	[46]
Signal transducer and activator of transcription 6 (STAT6)	OTCKMP49	STAT6_HUMAN	Affects Response To Substance	[45]
Transcription factor Jun (JUN)	OTCYBO6X	JUN_HUMAN	Increases ADR	[44]
Mitogen-activated protein kinase 8 (MAPK8)	OTEREYS5	MK08_HUMAN	Increases ADR	[44]
Platelet-derived growth factor subunit B (PDGFB)	OTMFMFC3	PDGFB_HUMAN	Decreases Response To Substance	[47]
Cholinesterase (BCHE)	OTOH3WQ9	CHLE_HUMAN	Increases Chemical Synthesis	[42]

References

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• [5] Morphine FDA Label
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