Details of the Drug Combination

General Information of Drug Combination (ID: DCC5670)

Drug Combination Name
Dexmedetomidine Enalaprilat
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Dexmedetomidine   DM93L4X Enalaprilat   DMFYAM1
Small molecular drug N.A.
2D MOL 2D MOL
3D MOL 3D MOL is unavailable
High-throughput Screening Result Testing Cell Line: KBM-7
Zero Interaction Potency (ZIP) Score: 12.8
Bliss Independence Score: 12.8
Loewe Additivity Score: 25.81
LHighest Single Agent (HSA) Score: 25.82

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Dexmedetomidine
Disease Entry ICD 11 Status REF
Irritability MB24 Approved [2]
Obstructive sleep apnea 7A41 Approved [3]
Traumatic brain injury NA07.Z Approved [3]
Respiratory failure CB41 Investigative [3]
Dexmedetomidine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Adrenergic receptor Alpha-2 (ADRA2) TTQ8AFT NOUNIPROTAC Agonist [6]
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Dexmedetomidine Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [7]
Cytochrome P450 2A6 (CYP2A6) DEJVYAZ CP2A6_HUMAN Metabolism [8]
Cytochrome P450 2E1 (CYP2E1) DEVDYN7 CP2E1_HUMAN Metabolism [9]
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Indication(s) of Enalaprilat
Disease Entry ICD 11 Status REF
Congestive heart failure BD10 Approved [4]
Hypertension BA00-BA04 Approved [5]
Malignant essential hypertension BA00 Approved [4]
Enalaprilat Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Angiotensin-converting enzyme (ACE) TTL69WB ACE_HUMAN Inhibitor [10]
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Enalaprilat Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Peptide transporter 1 (SLC15A1) DT9G7XN S15A1_HUMAN Substrate [11]
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Enalaprilat Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Dipeptidase (pepV) DEQMBHW Q84BU9_LACLH Metabolism [12]
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Enalaprilat Interacts with 5 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Endothelin-1 (EDN1) OTZCACEG EDN1_HUMAN Decreases Secretion [13]
B1 bradykinin receptor (BDKRB1) OT1DHSVQ BKRB1_HUMAN Increases Activity [14]
Organic anion transporter 3 (SLC22A8) OT8BY933 S22A8_HUMAN Increases Uptake [15]
Solute carrier family 22 member 11 (SLC22A11) OTAJLNJZ S22AB_HUMAN Increases Uptake [15]
Solute carrier organic anion transporter family member 1B1 (SLCO1B1) OTNEN8QK SO1B1_HUMAN Affects Abundance [16]
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References

1 Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
2 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: 521).
3 Dexmedetomidine FDA Label
4 Enalaprilat FDA Label
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: 6332).
6 Dexmedetomidine in intensive care unit: a study of hemodynamic changes. Middle East J Anesthesiol. 2002 Oct;16(6):587-95.
7 Predominant role of peripheral catecholamines in the stress-induced modulation of CYP1A2 inducibility by benzo(alpha)pyrene. Basic Clin Pharmacol Toxicol. 2008 Jan;102(1):35-44.
8 Impact of CYP2A6 gene polymorphism on the pharmacokinetics of dexmedetomidine for premedication. Expert Rev Clin Pharmacol. 2018 Sep;11(9):917-922.
9 Metabolic stability and determination of cytochrome P450 isoenzymes' contribution to the metabolism of medetomidine in dog liver microsomes. Biomed Chromatogr. 2010 Aug;24(8):868-77.
10 Analysis of Vancomycin in the Hindlimb Vascular Bed of the Rat. Am J Ther. 1996 Oct;3(10):681-687.
11 Transporter-mediated Drug Interactions. Drug Metab Pharmacokinet. 2002;17(4):253-74.
12 Characterization and kinetic analysis of enzyme-substrate recognition by three recombinant lactococcal PepVs. Arch Biochem Biophys. 2006 Oct 15;454(2):137-45.
13 Different effects of angiotensin converting enzyme inhibitors on endothelin-1 and nitric oxide balance in human vascular endothelial cells: evidence of an oxidant-sensitive pathway. Mediators Inflamm. 2008;2008:305087. doi: 10.1155/2008/305087. Epub 2008 Dec 1.
14 Novel mode of action of angiotensin I converting enzyme inhibitors: direct activation of bradykinin B1 receptor. J Biol Chem. 2002 May 10;277(19):16847-52. doi: 10.1074/jbc.M200355200. Epub 2002 Mar 5.
15 Completing the Enalaprilat Excretion Pathway-Renal Handling by the Proximal Tubule. Pharmaceutics. 2020 Sep 30;12(10):935. doi: 10.3390/pharmaceutics12100935.
16 Effect of organic anion-transporting polypeptide 1B1 (OATP1B1) polymorphism on the single- and multiple-dose pharmacokinetics of enalapril in healthy Chinese adult men. Clin Ther. 2011 May;33(5):655-63. doi: 10.1016/j.clinthera.2011.04.018.