Details of the Drug Combination

General Information of Drug Combination (ID: DC0L4XA)

Drug Combination Name
Enalaprilat Maprotiline
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Enalaprilat   DMFYAM1 Maprotiline   DMPWB7T
N.A. Small molecular drug
2D MOL 2D MOL
3D MOL is unavailable 3D MOL
High-throughput Screening Result Testing Cell Line: KBM-7
Zero Interaction Potency (ZIP) Score: 0.73
Bliss Independence Score: 0.73
Loewe Additivity Score: 1.55
LHighest Single Agent (HSA) Score: 1.55

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Enalaprilat
Disease Entry ICD 11 Status REF
Congestive heart failure BD10 Approved [2]
Hypertension BA00-BA04 Approved [3]
Malignant essential hypertension BA00 Approved [2]
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 [6]
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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 [7]
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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 [8]
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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 [9]
B1 bradykinin receptor (BDKRB1) OT1DHSVQ BKRB1_HUMAN Increases Activity [10]
Organic anion transporter 3 (SLC22A8) OT8BY933 S22A8_HUMAN Increases Uptake [11]
Solute carrier family 22 member 11 (SLC22A11) OTAJLNJZ S22AB_HUMAN Increases Uptake [11]
Solute carrier organic anion transporter family member 1B1 (SLCO1B1) OTNEN8QK SO1B1_HUMAN Affects Abundance [12]
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Indication(s) of Maprotiline
Disease Entry ICD 11 Status REF
Depression 6A70-6A7Z Approved [4]
Major depressive disorder 6A70.3 Approved [5]
Mixed anxiety and depressive disorder N.A. Investigative [4]
Maprotiline Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Norepinephrine transporter (NET) TTAWNKZ SC6A2_HUMAN Inhibitor [13]
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Maprotiline Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [14]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [14]
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Maprotiline Interacts with 2 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 2D6 (CYP2D6) OTZJC802 CP2D6_HUMAN Increases ADR [15]
Beclin-1 (BECN1) OT4X293M BECN1_HUMAN Increases Expression [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 Enalaprilat 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: 6332).
4 Maprotiline FDA Label
5 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
6 Analysis of Vancomycin in the Hindlimb Vascular Bed of the Rat. Am J Ther. 1996 Oct;3(10):681-687.
7 Transporter-mediated Drug Interactions. Drug Metab Pharmacokinet. 2002;17(4):253-74.
8 Characterization and kinetic analysis of enzyme-substrate recognition by three recombinant lactococcal PepVs. Arch Biochem Biophys. 2006 Oct 15;454(2):137-45.
9 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.
10 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.
11 Completing the Enalaprilat Excretion Pathway-Renal Handling by the Proximal Tubule. Pharmaceutics. 2020 Sep 30;12(10):935. doi: 10.3390/pharmaceutics12100935.
12 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.
13 Effect of pharmacologically selective antidepressants on serotonin uptake in rat platelets. Gen Physiol Biophys. 2005 Mar;24(1):113-28.
14 Cytochrome P450 enzymes contributing to demethylation of maprotiline in man. Pharmacol Toxicol. 2002 Mar;90(3):144-9.
15 ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
16 The antidepressants maprotiline and fluoxetine induce Type II autophagic cell death in drug-resistant Burkitt's lymphoma. Int J Cancer. 2011 Apr 1;128(7):1712-23. doi: 10.1002/ijc.25477. Epub 2010 May 25.