General Information of Drug Combination (ID: DCKJ3FU)

Drug Combination Name
Eptifibatide Imipramine
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Eptifibatide   DMQXTJS Imipramine   DM2NUH3
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: KBM-7
Zero Interaction Potency (ZIP) Score: 8.69
Bliss Independence Score: 8.69
Loewe Additivity Score: 23.82
LHighest Single Agent (HSA) Score: 23.84

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Eptifibatide
Disease Entry ICD 11 Status REF
Acute cardiac ischemic events BA40.Z Approved [2]
Acute coronary syndrome BA41 Approved [3]
Pneumonia CA40 Approved [3]
Eptifibatide Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Glycoprotein IIb/IIIa receptor (GPIIb/IIIa) TT38RM1 ITA2B_HUMAN; ITB3_HUMAN Modulator [6]
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Eptifibatide Interacts with 4 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Prothrombin (F2) OTNFSM49 THRB_HUMAN Increases Expression [7]
C-reactive protein (CRP) OT0RFT8F CRP_HUMAN Increases Expression [7]
CD40 ligand (CD40LG) OT75Z6A6 CD40L_HUMAN Decreases Expression [7]
Integrin alpha-IIb (ITGA2B) OT4Y17PY ITA2B_HUMAN Increases ADR [8]
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Indication(s) of Imipramine
Disease Entry ICD 11 Status REF
Depression 6A70-6A7Z Approved [4]
Nocturia MF55 Approved [5]
Imipramine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Norepinephrine transporter (NET) TTAWNKZ SC6A2_HUMAN Inhibitor [11]
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Imipramine Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [12]
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Imipramine Interacts with 9 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [13]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [14]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Metabolism [15]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [16]
Cytochrome P450 3A7 (CYP3A7) DERD86B CP3A7_HUMAN Metabolism [17]
Cytochrome P450 2C18 (CYP2C18) DEZMWRE CP2CI_HUMAN Metabolism [14]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Metabolism [14]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [18]
Docosahexaenoic acid omega-hydroxylase (CYP4F11) DEIZLTN CP4FB_HUMAN Metabolism [19]
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⏷ Show the Full List of 9 DME(s)
Imipramine Interacts with 19 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Nuclear protein 1 (NUPR1) OT4FU8C0 NUPR1_HUMAN Increases Expression [9]
Alpha-1-antichymotrypsin (SERPINA3) OT9BP2S0 AACT_HUMAN Increases Expression [9]
Solute carrier family 2, facilitated glucose transporter member 3 (SLC2A3) OT2HZK5M GTR3_HUMAN Decreases Expression [9]
Inhibin beta E chain (INHBE) OTOI2NYG INHBE_HUMAN Increases Expression [9]
Acid ceramidase (ASAH1) OT1DNGXL ASAH1_HUMAN Increases Expression [9]
Nuclear receptor subfamily 0 group B member 2 (NR0B2) OT7UVICX NR0B2_HUMAN Increases Expression [9]
Lysophospholipase D GDPD3 (GDPD3) OTOHM9QM GDPD3_HUMAN Increases Expression [9]
Fibronectin type III domain-containing protein 4 (FNDC4) OTOQK0WK FNDC4_HUMAN Increases Expression [9]
Protein DEPP1 (DEPP1) OTB36PHJ DEPP1_HUMAN Increases Expression [9]
Stearoyl-CoA desaturase (SCD) OTB1073G SCD_HUMAN Increases Expression [20]
Albumin (ALB) OTVMM513 ALBU_HUMAN Affects Binding [21]
Beta-2 adrenergic receptor (ADRB2) OTSDOX4Q ADRB2_HUMAN Decreases Expression [22]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [23]
Alpha-1-acid glycoprotein 2 (ORM2) OTRJGZP8 A1AG2_HUMAN Affects Binding [24]
Heat shock factor protein 1 (HSF1) OTYNJ4KP HSF1_HUMAN Decreases Activity [25]
Hydroxymethylglutaryl-CoA synthase, cytoplasmic (HMGCS1) OTCO26FV HMCS1_HUMAN Increases Expression [20]
Multidrug and toxin extrusion protein 1 (SLC47A1) OTZX0U5Q S47A1_HUMAN Decreases Activity [26]
DnaJ homolog subfamily C member 5 (DNAJC5) OTCZDXAL DNJC5_HUMAN Increases Expression [27]
SH3 and multiple ankyrin repeat domains protein 2 (SHANK2) OTSQTPFQ SHAN2_HUMAN Decreases Expression [28]
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⏷ Show the Full List of 19 DOT(s)

References

1 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
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: 6585).
3 Eptifibatide FDA Label
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: 357).
5 Imipramine FDA Label
6 Barbourin. A GPIIb-IIIa-specific integrin antagonist from the venom of Sistrurus m. barbouri. J Biol Chem. 1991 May 25;266(15):9359-62.
7 Eptifibatide in peripheral vascular interventions: results of the Integrilin Reduces Inflammation in Peripheral Vascular Interventions (INFLAME) trial. J Invasive Cardiol. 2006 Jan;18(1):6-12.
8 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.
9 A toxicogenomic approach to drug-induced phospholipidosis: analysis of its induction mechanism and establishment of a novel in vitro screening system. Toxicol Sci. 2005 Feb;83(2):282-92.
10 N-glucuronidation of nicotine and cotinine by human liver microsomes and heterologously expressed UDP-glucuronosyltransferases. Drug Metab Dispos. 2003 Nov;31(11):1361-8. doi: 10.1124/dmd.31.11.1361.
11 Invivo antioxidant status: a putative target of antidepressant action. Prog Neuropsychopharmacol Biol Psychiatry. 2009 Mar 17;33(2):220-8.
12 Caco-2 permeability, P-glycoprotein transport ratios and brain penetration of heterocyclic drugs. Int J Pharm. 2003 Sep 16;263(1-2):113-22.
13 Variability in metabolism of imipramine and desipramine using urinary excretion data. J Anal Toxicol. 2014 Jul-Aug;38(6):368-74.
14 Reappraisal of human CYP isoforms involved in imipramine N-demethylation and 2-hydroxylation: a study using microsomes obtained from putative extensive and poor metabolizers of S-mephenytoin and eleven recombinant human CYPs. J Pharmacol Exp Ther. 1997 Jun;281(3):1199-210.
15 Liquid chromatography-tandem mass spectrometry method for measurement of nicotine N-glucuronide: a marker for human UGT2B10 inhibition. J Pharm Biomed Anal. 2011 Jul 15;55(5):964-71.
16 QTc prolongation associated with combination therapy of levofloxacin, imipramine, and fluoxetine. Ann Pharmacother. 2005 Mar;39(3):543-6.
17 Catalysis of drug oxidation during embryogenesis in human hepatic tissues using imipramine as a model substrate. Drug Metab Dispos. 1999 Nov;27(11):1306-8.
18 Inhibitory effects of tricyclic antidepressants (TCAs) on human cytochrome P450 enzymes in vitro: mechanism of drug interaction between TCAs and phenytoin. Drug Metab Dispos. 2002 Oct;30(10):1102-7.
19 Expression and characterization of human cytochrome P450 4F11: putative role in the metabolism of therapeutic drugs and eicosanoids. Toxicol Appl Pharmacol. 2004 Sep 15;199(3):295-304.
20 Antidepressant drugs activate SREBP and up-regulate cholesterol and fatty acid biosynthesis in human glial cells. Neurosci Lett. 2006 Mar 13;395(3):185-90. doi: 10.1016/j.neulet.2005.10.096. Epub 2005 Dec 1.
21 Use of peak decay analysis and affinity microcolumns containing silica monoliths for rapid determination of drug-protein dissociation rates. J Chromatogr A. 2011 Apr 15;1218(15):2072-8. doi: 10.1016/j.chroma.2010.09.070. Epub 2010 Oct 16.
22 Neutrophil beta(2)-adrenoceptor function in major depression: G(s) coupling, effects of imipramine and relationship to treatment outcome. Eur J Pharmacol. 1999 Dec 15;386(2-3):135-44. doi: 10.1016/s0014-2999(99)00749-9.
23 The antidepressants imipramine, clomipramine, and citalopram induce apoptosis in human acute myeloid leukemia HL-60 cells via caspase-3 activation. J Biochem Mol Toxicol. 1999;13(6):338-47. doi: 10.1002/(sici)1099-0461(1999)13:6<338::aid-jbt8>3.0.co;2-7.
24 Binding of disopyramide, methadone, dipyridamole, chlorpromazine, lignocaine and progesterone to the two main genetic variants of human alpha 1-acid glycoprotein: evidence for drug-binding differences between the variants and for the presence of two separate drug-binding sites on alpha 1-acid glycoprotein. Pharmacogenetics. 1996 Oct;6(5):403-15. doi: 10.1097/00008571-199610000-00004.
25 A Gene Expression Biomarker Predicts Heat Shock Factor 1 Activation in a Gene Expression Compendium. Chem Res Toxicol. 2021 Jul 19;34(7):1721-1737. doi: 10.1021/acs.chemrestox.0c00510. Epub 2021 Jun 25.
26 Molecular identification and functional characterization of rat multidrug and toxin extrusion type transporter 1 as an organic cation/H+ antiporter in the kidney. Drug Metab Dispos. 2006 Nov;34(11):1868-74. doi: 10.1124/dmd.106.010876. Epub 2006 Aug 23.
27 Induction of cysteine string protein after chronic antidepressant treatment in rat frontal cortex. Neurosci Lett. 2001 Apr 6;301(3):183-6. doi: 10.1016/s0304-3940(01)01638-x.
28 Establishment of a 13 genes-based molecular prediction score model to discriminate the neurotoxic potential of food relevant-chemicals. Toxicol Lett. 2022 Feb 1;355:1-18. doi: 10.1016/j.toxlet.2021.10.013. Epub 2021 Nov 5.