Details of the Drug Combination

General Information of Drug Combination (ID: DCMP1JA)

• Drug Combination Name: Clonidine + Sevoflurane
• Indication: Surgery; Status: Phase 1 [1]
• Component Drugs:
  Clonidine (DM6RZ9Q): Small molecular drug
  Sevoflurane (DMC9O43): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Clonidine

Disease Entry	ICD 11	Status	REF
Attention deficit hyperactivity disorder	6A05.Z	Approved	[2]
Hypertension	BA00-BA04	Approved	[3]
Neonatal abstinence syndrome	N.A.	Approved	[2]
Diabetic neuropathy	8C0Z	Phase 3	[4]

Clonidine Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Adrenergic receptor Alpha-2 (ADRA2)	TTQ8AFT	NOUNIPROTAC	Agonist	[7]
Membrane copper amine oxidase (AOC3)	TT7HC21	AOC3_HUMAN	Inhibitor	[8]

Clonidine Interacts with 4 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[9]
Organic cation transporter 2 (SLC22A2)	DT9IDPW	S22A2_HUMAN	Substrate	[10]
Organic cation transporter 3 (SLC22A3)	DT6201N	S22A3_HUMAN	Substrate	[10]
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[10]

Clonidine Interacts with 4 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	[11]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[11]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[11]

Clonidine Interacts with 24 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases ADR	[12]
Cytochrome P450 1A2 (CYP1A2)	OTLLBX48	CP1A2_HUMAN	Increases ADR	[12]
G protein-activated inward rectifier potassium channel 1 (KCNJ3)	OTHQG16J	KCNJ3_HUMAN	Increases ADR	[12]
Apoptosis-inducing factor 1, mitochondrial (AIFM1)	OTKPWB7Q	AIFM1_HUMAN	Increases Expression	[13]
Renin (REN)	OT52GZR2	RENI_HUMAN	Decreases Activity	[14]
Pro-opiomelanocortin (POMC)	OTV41F7T	COLI_HUMAN	Increases Expression	[15]
Prolactin (PRL)	OTWFQGX7	PRL_HUMAN	Increases Expression	[16]
Somatotropin (GH1)	OT92RTRD	SOMA_HUMAN	Increases Expression	[17]
Insulin (INS)	OTZ85PDU	INS_HUMAN	Decreases Secretion	[18]
Apolipoprotein A-I (APOA1)	OT5THARI	APOA1_HUMAN	Decreases Expression	[19]
Apolipoprotein A-II (APOA2)	OTQ3HGTC	APOA2_HUMAN	Decreases Expression	[19]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[13]
Tumor necrosis factor alpha-induced protein 3 (TNFAIP3)	OTVLI4DD	TNAP3_HUMAN	Increases Expression	[20]
Interleukin-10 (IL10)	OTIRFRXC	IL10_HUMAN	Increases Secretion	[21]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[13]
Caspase-2 (CASP2)	OTUDYSPP	CASP2_HUMAN	Increases Activity	[13]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Activity	[13]
Tumor protein D52 (TPD52)	OTPKSK43	TPD52_HUMAN	Increases Expression	[20]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Increases Activity	[13]
Programmed cell death protein 4 (PDCD4)	OTZ6NXUX	PDCD4_HUMAN	Decreases Expression	[20]
Bcl2-associated agonist of cell death (BAD)	OT63ERYM	BAD_HUMAN	Increases Expression	[13]
Delta-type opioid receptor (OPRD1)	OT164PA1	OPRD_HUMAN	Increases ADR	[12]
Myeloperoxidase (MPO)	OTOOXLIN	PERM_HUMAN	Increases ADR	[12]
Kappa-type opioid receptor (OPRK1)	OTXCZF4L	OPRK_HUMAN	Increases ADR	[12]

Indication(s) of Sevoflurane

Disease Entry	ICD 11	Status	REF
Anaesthesia	9A78.6	Approved	[5]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 3	[6]

Sevoflurane Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Glutamate receptor AMPA (GRIA)	TTAN6JD	NOUNIPROTAC	Antagonist	[22]

Sevoflurane Interacts with 4 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[23]
Cytochrome P450 2A6 (CYP2A6)	DEJVYAZ	CP2A6_HUMAN	Metabolism	[24]
Cytochrome P450 2E1 (CYP2E1)	DEVDYN7	CP2E1_HUMAN	Metabolism	[25]
Cytochrome P450 2B6 (CYP2B6)	DEPKLMQ	CP2B6_HUMAN	Metabolism	[26]

Sevoflurane Interacts with 60 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Expression	[27]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[28]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[28]
Glycine receptor subunit alpha-1 (GLRA1)	OT05Y9ZR	GLRA1_HUMAN	Increases ADR	[12]
Glutamate dehydrogenase 1, mitochondrial (GLUD1)	OTXKOCUH	DHE3_HUMAN	Increases Expression	[29]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Increases Expression	[30]
GTPase HRas (HRAS)	OTWQN0DP	RASH_HUMAN	Increases Expression	[30]
GTPase KRas (KRAS)	OT78QCN8	RASK_HUMAN	Decreases Expression	[30]
Progonadoliberin-1 (GNRH1)	OTH8A44K	GON1_HUMAN	Increases Expression	[30]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Increases Expression	[30]
Fibronectin (FN1)	OTB5ZN4Q	FINC_HUMAN	Increases Expression	[30]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Expression	[27]
Insulin-like growth factor I (IGF1)	OTIIZR61	IGF1_HUMAN	Increases Expression	[30]
Amyloid-beta precursor protein (APP)	OTKFD7R4	A4_HUMAN	Increases Expression	[31]
Integrin beta-3 (ITGB3)	OTWCK1K6	ITB3_HUMAN	Decreases Expression	[30]
Hepatocyte growth factor receptor (MET)	OT7K55MU	MET_HUMAN	Increases Expression	[30]
Solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1)	OTA675TJ	GTR1_HUMAN	Increases Expression	[29]
Cadherin-1 (CDH1)	OTFJMXPM	CADH1_HUMAN	Decreases Expression	[30]
Proto-oncogene tyrosine-protein kinase Src (SRC)	OTETYX40	SRC_HUMAN	Increases Expression	[30]
Hepatocyte growth factor (HGF)	OTGHUA23	HGF_HUMAN	Increases Expression	[30]
Matrix metalloproteinase-9 (MMP9)	OTB2QDAV	MMP9_HUMAN	Increases Expression	[30]
Cyclic AMP-dependent transcription factor ATF-2 (ATF2)	OTNIZPEA	ATF2_HUMAN	Increases Phosphorylation	[32]
Sphingomyelin phosphodiesterase (SMPD1)	OTZSMA54	ASM_HUMAN	Decreases Activity	[27]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Increases Phosphorylation	[29]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Increases Phosphorylation	[29]
Ephrin type-B receptor 2 (EPHB2)	OT8VZ6C5	EPHB2_HUMAN	Increases Expression	[30]
Macrosialin (CD68)	OTOYEY3J	CD68_HUMAN	Increases Expression	[30]
Merlin (NF2)	OT6E5ACG	MERL_HUMAN	Increases Expression	[30]
Pigment epithelium-derived factor (SERPINF1)	OTWZH98J	PEDF_HUMAN	Decreases Expression	[29]
Serine/threonine-protein kinase mTOR (MTOR)	OTHH8KU7	MTOR_HUMAN	Decreases Phosphorylation	[28]
Cell surface glycoprotein MUC18 (MCAM)	OTT8XKGE	MUC18_HUMAN	Decreases Expression	[30]
Collagenase 3 (MMP13)	OTY8BZIE	MMP13_HUMAN	Increases Expression	[30]
Proliferation marker protein Ki-67 (MKI67)	OTA8N1QI	KI67_HUMAN	Increases Expression	[29]
Dual specificity mitogen-activated protein kinase kinase 3 (MAP2K3)	OTI2OREX	MP2K3_HUMAN	Increases Phosphorylation	[32]
Stromal cell-derived factor 1 (CXCL12)	OT2QX5LL	SDF1_HUMAN	Increases Expression	[29]
Dual specificity mitogen-activated protein kinase kinase 6 (MAP2K6)	OTK13JKC	MP2K6_HUMAN	Increases Phosphorylation	[32]
Caspase-7 (CASP7)	OTAPJ040	CASP7_HUMAN	Increases Activity	[33]
Beta-secretase 1 (BACE1)	OTCA7B6A	BACE1_HUMAN	Increases Expression	[31]
C-X-C chemokine receptor type 4 (CXCR4)	OTUFSBX2	CXCR4_HUMAN	Increases Expression	[29]
Protein SET (SET)	OTGYYQJO	SET_HUMAN	Increases Expression	[30]
RNA-binding protein EWS (EWSR1)	OT7SRHV3	EWS_HUMAN	Increases Expression	[30]
Urokinase plasminogen activator surface receptor (PLAUR)	OTIRKKEQ	UPAR_HUMAN	Increases Expression	[30]
Alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase A (MGAT5)	OTU4DD4G	MGT5A_HUMAN	Increases Expression	[30]
Metastasis-associated protein MTA1 (MTA1)	OTBHW3S9	MTA1_HUMAN	Increases Expression	[30]
Sequestosome-1 (SQSTM1)	OTGY5D5J	SQSTM_HUMAN	Decreases Expression	[28]
Integrin alpha-7 (ITGA7)	OTTBTAYW	ITA7_HUMAN	Decreases Expression	[30]
Interleukin-18 (IL18)	OTBB2A8O	IL18_HUMAN	Increases Expression	[30]
Metastasis-suppressor KiSS-1 (KISS1)	OT6IE3K2	KISS1_HUMAN	Decreases Expression	[30]
Mothers against decapentaplegic homolog 2 (SMAD2)	OTC6VB4K	SMAD2_HUMAN	Increases Expression	[30]
Hypoxia-inducible factor 1-alpha (HIF1A)	OTADSC03	HIF1A_HUMAN	Increases Expression	[30]
KiSS-1 receptor (KISS1R)	OTQA3J6G	KISSR_HUMAN	Decreases Expression	[30]
FXYD domain-containing ion transport regulator 5 (FXYD5)	OT81DIOD	FXYD5_HUMAN	Increases Expression	[30]
Mitogen-activated protein kinase kinase kinase 5 (MAP3K5)	OTQR6ENW	M3K5_HUMAN	Increases Phosphorylation	[32]
Oxidoreductase HTATIP2 (HTATIP2)	OT9MZ4QO	HTAI2_HUMAN	Increases Expression	[30]
Microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B)	OTUYHB84	MLP3B_HUMAN	Increases Lipidation	[28]
Autophagy protein 5 (ATG5)	OT4T5SMS	ATG5_HUMAN	Increases Expression	[28]
Pinin (PNN)	OT0HXICH	PININ_HUMAN	Increases Expression	[30]
Programmed cell death 1 ligand 1 (CD274)	OTJ0VFDL	PD1L1_HUMAN	Decreases Expression	[34]
Heparanase (HPSE)	OTPTK5VS	HPSE_HUMAN	Increases Expression	[30]
Mitochondrial pyruvate carrier 1 (MPC1)	OT6DYFUO	MPC1_HUMAN	Increases Expression	[29]

References

• [1] ClinicalTrials.gov (NCT06287151) Regional Anesthesia EMG Study
• [2] Clonidine FDA Label
• [3] 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: 516).
• [4] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [5] 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: 7296).
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