General Information of Drug Combination (ID: DCH6BK8)

Drug Combination Name
Propranolol Oxytocin
Indication
Disease Entry Status REF
Postpartum Hemorrhage Phase 1 [1]
Component Drugs Propranolol   DM79NTF Oxytocin   DMDL27I
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Propranolol
Disease Entry ICD 11 Status REF
Angina pectoris BA40 Approved [2]
Atrial fibrillation BC81.3 Approved [2]
Cocaine addiction 6C45.2 Approved [2]
Hemangioma 2E81-2F2Y Approved [2]
Migraine 8A80 Approved [3]
Respiratory papillomatosis 2F00.1 Investigative [2]
Propranolol Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Adrenergic receptor beta-1 (ADRB1) TTR6W5O ADRB1_HUMAN Antagonist [9]
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Propranolol Interacts with 4 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [10]
Organic cation transporter 2 (SLC22A2) DT9IDPW S22A2_HUMAN Substrate [11]
Organic cation transporter 3 (SLC22A3) DT6201N S22A3_HUMAN Substrate [11]
Organic cation transporter 1 (SLC22A1) DTT79CX S22A1_HUMAN Substrate [11]
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Propranolol Interacts with 8 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [12]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [13]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [14]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [15]
Cytochrome P450 3A7 (CYP3A7) DERD86B CP3A7_HUMAN Metabolism [15]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [16]
Dimethylaniline oxidase 2 (FMO2) DEIASEZ FMO2_HUMAN Metabolism [17]
Cytochrome P450 102A1 (cyp102) DE4OGUF CPXB_BACMB Metabolism [18]
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⏷ Show the Full List of 8 DME(s)
Propranolol Interacts with 34 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases Oxidation [19]
Cytochrome P450 2C19 (CYP2C19) OTFMJYYE CP2CJ_HUMAN Increases Oxidation [19]
Flavin-containing monooxygenase 2 (FMO2) OTUJUL9S FMO2_HUMAN Increases Oxidation [17]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Expression [20]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [21]
Potassium voltage-gated channel subfamily KQT member 1 (KCNQ1) OT8SPJNX KCNQ1_HUMAN Affects Response To Substance [22]
72 kDa type IV collagenase (MMP2) OT5NIWA2 MMP2_HUMAN Decreases Expression [8]
Matrix metalloproteinase-9 (MMP9) OTB2QDAV MMP9_HUMAN Decreases Expression [8]
Prostaglandin G/H synthase 2 (PTGS2) OT75U9M4 PGH2_HUMAN Decreases Expression [8]
Angiopoietin-2 (ANGPT2) OTEQK65P ANGP2_HUMAN Decreases Expression [23]
Nuclear receptor subfamily 1 group I member 2 (NR1I2) OTC5U0N5 NR1I2_HUMAN Increases Activity [24]
Renin (REN) OT52GZR2 RENI_HUMAN Decreases Activity [25]
Angiotensinogen (AGT) OTBZLYR3 ANGT_HUMAN Decreases Expression [26]
Insulin (INS) OTZ85PDU INS_HUMAN Decreases Expression [27]
Beta-2 adrenergic receptor (ADRB2) OTSDOX4Q ADRB2_HUMAN Decreases Expression [28]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [23]
Ornithine decarboxylase (ODC1) OTNDAGRR DCOR_HUMAN Increases Activity [29]
Beta-adrenergic receptor kinase 1 (GRK2) OT34KKWK ARBK1_HUMAN Decreases Expression [30]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Phosphorylation [31]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [32]
Proliferation marker protein Ki-67 (MKI67) OTA8N1QI KI67_HUMAN Decreases Expression [23]
Neurogenic locus notch homolog protein 1 (NOTCH1) OTI1WADQ NOTC1_HUMAN Decreases Expression [31]
G protein-activated inward rectifier potassium channel 1 (KCNJ3) OTHQG16J KCNJ3_HUMAN Increases Expression [28]
Caspase-7 (CASP7) OTAPJ040 CASP7_HUMAN Increases Activity [32]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Cleavage [33]
ADP-ribosylation factor 6 (ARF6) OTVV7KJO ARF6_HUMAN Affects Localization [34]
Angiopoietin-1 receptor (TEK) OT78YN57 TIE2_HUMAN Decreases Expression [23]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [23]
Delta-like protein 4 (DLL4) OTRA4K2V DLL4_HUMAN Decreases Expression [31]
Inward rectifier potassium channel 2 (KCNJ2) OT2OQEZS KCNJ2_HUMAN Affects Response To Substance [22]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Increases ADR [35]
Cytochrome P450 2C9 (CYP2C9) OTGLBN29 CP2C9_HUMAN Increases Oxidation [19]
Sodium channel protein type 5 subunit alpha (SCN5A) OTGYZWR6 SCN5A_HUMAN Increases ADR [35]
Potassium voltage-gated channel subfamily E member 1 (KCNE1) OTZNQUW9 KCNE1_HUMAN Increases ADR [35]
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⏷ Show the Full List of 34 DOT(s)
Indication(s) of Oxytocin
Disease Entry ICD 11 Status REF
Autism spectrum disorder 6A02 Approved [4]
Ductal breast carcinoma in situ N.A. Approved [5]
Postpartum haemorrhage JA43 Approved [5]
Lactation failure JB46.3 Phase 3 [6]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 2 [7]
Oxytocin Interacts with 4 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Vasopressin V1b receptor (V1BR) TTL9MHW V1BR_HUMAN Agonist [36]
Vasopressin V2 receptor (V2R) TTK8R02 V2R_HUMAN Agonist [37]
Vasopressin V1a receptor (V1AR) TT4TFGN V1AR_HUMAN Agonist [38]
Oxytocin receptor (OTR) TTSCIUP OXYR_HUMAN Modulator [39]
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Oxytocin Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Krueppel-like factor 4 (KLF4) OT4O9RQW KLF4_HUMAN Increases Expression [40]
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Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Poor; Labor DCRWUJM N. A. Phase 3 [41]
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References

1 ClinicalTrials.gov (NCT03434444) In Vitro Optimization of Oxytocin-induced Myometrial Contractility by Propranolol
2 Propranolol 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: 7596).
4 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: 2174).
5 Oxytocin FDA Label
6 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800039450)
7 Phase II RCT to Assess Efficacy of Intravenous Administration of Oxytocin in Patients Affected by COVID-19 (OsCOVID19)
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13 Synthetic and natural compounds that interact with human cytochrome P450 1A2 and implications in drug development. Curr Med Chem. 2009;16(31):4066-218.
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15 The influence of diltiazem versus cimetidine on propranolol metabolism. J Clin Pharmacol. 1992 Dec;32(12):1099-104.
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17 Human FMO2-based microbial whole-cell catalysts for drug metabolite synthesis. Microb Cell Fact. 2015 Jun 12;14:82.
18 acillus megaterium SF185 spores exert protective effects against oxidative stress in vivo and in vitro. Sci Rep. 2019 Aug 19;9(1):12082.
19 Comparative study of the oxidation of propranolol enantiomers in hepatic and small intestinal microsomes from cynomolgus and marmoset monkeys. Chem Biol Interact. 2010 Jan 5;183(1):67-78. doi: 10.1016/j.cbi.2009.10.007.
20 Rapid induction of P-glycoprotein expression by high permeability compounds in colonic cells in vitro: a possible source of transporter mediated drug interactions?. Biochem Pharmacol. 2004 Aug 15;68(4):783-90. doi: 10.1016/j.bcp.2004.05.006.
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23 Propranolol inhibits proliferation and induces apoptosis of hemangioma-derived endothelial cells via Akt pathway by down-regulating Ang-2 expression. Chem Biol Interact. 2020 Jan 25;316:108925. doi: 10.1016/j.cbi.2019.108925. Epub 2019 Dec 12.
24 Development of a common carp (Cyprinus carpio) pregnane X receptor (cPXR) transactivation reporter assay and its activation by azole fungicides and pharmaceutical chemicals. Toxicol In Vitro. 2017 Jun;41:114-122. doi: 10.1016/j.tiv.2017.02.023. Epub 2017 Mar 1.
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30 Reciprocal in vivo regulation of myocardial G protein-coupled receptor kinase expression by beta-adrenergic receptor stimulation and blockade. Circulation. 1998 Oct 27;98(17):1783-9. doi: 10.1161/01.cir.98.17.1783.
31 Propranolol inhibits proliferation and invasion of hemangioma-derived endothelial cells by suppressing the DLL4/Notch1/Akt pathway. Chem Biol Interact. 2018 Oct 1;294:28-33. doi: 10.1016/j.cbi.2018.08.018. Epub 2018 Aug 18.
32 Palmitate increases the susceptibility of cells to drug-induced toxicity: an in vitro method to identify drugs with potential contraindications in patients with metabolic disease. Toxicol Sci. 2012 Oct;129(2):346-62. doi: 10.1093/toxsci/kfs208. Epub 2012 Jun 14.
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34 An effector domain mutant of Arf6 implicates phospholipase D in endosomal membrane recycling. Mol Biol Cell. 2006 Jan;17(1):327-35. doi: 10.1091/mbc.e05-06-0523. Epub 2005 Nov 9.
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40 Oxytocin inhibits ox-LDL-induced adhesion of monocytic THP-1 cells to human brain microvascular endothelial cells. Toxicol Appl Pharmacol. 2017 Dec 15;337:104-110. doi: 10.1016/j.taap.2017.10.022. Epub 2017 Nov 2.
41 ClinicalTrials.gov (NCT02702674) The Effect of Coadministration of Oral Propranolol to Oxytocin on Induction of Labor