General Information of Drug Combination (ID: DC6HVZG)

Drug Combination Name
Diazoxide Imipramine
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Diazoxide   DML1538 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: 0.86
Bliss Independence Score: 0.86
Loewe Additivity Score: 1.29
LHighest Single Agent (HSA) Score: 1.3

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Diazoxide
Disease Entry ICD 11 Status REF
Congenital hyperinsulinism 5A4Y Approved [2]
Hyperinsulinemia 5A4Y Approved [2]
Hypertension BA00-BA04 Approved [3]
Hypertensive emergency BA03 Approved [2]
Insulinoma 2C10.1 Approved [2]
Malignant essential hypertension BA00 Approved [2]
Diazoxide Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Potassium channel unspecific (KC) TT1VOHK NOUNIPROTAC Modulator [6]
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Diazoxide Interacts with 8 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Decreases Secretion [7]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Decreases Secretion [7]
Nuclear factor NF-kappa-B p105 subunit (NFKB1) OTNRRD8I NFKB1_HUMAN Increases Activity [8]
Interleukin-10 (IL10) OTIRFRXC IL10_HUMAN Decreases Secretion [7]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Decreases Expression [9]
Catenin beta-1 (CTNNB1) OTZ932A3 CTNB1_HUMAN Decreases Expression [9]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Increases Expression [8]
ATP-sensitive inward rectifier potassium channel 11 (KCNJ11) OTPUUELV KCJ11_HUMAN Decreases Expression [10]
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⏷ Show the Full List of 8 DOT(s)
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 [13]
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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 [14]
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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 [15]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [16]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Metabolism [17]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [18]
Cytochrome P450 3A7 (CYP3A7) DERD86B CP3A7_HUMAN Metabolism [19]
Cytochrome P450 2C18 (CYP2C18) DEZMWRE CP2CI_HUMAN Metabolism [16]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Metabolism [16]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [20]
Docosahexaenoic acid omega-hydroxylase (CYP4F11) DEIZLTN CP4FB_HUMAN Metabolism [21]
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⏷ Show the Full List of 9 DME(s)
Imipramine Interacts with 32 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Glutathione S-transferase P (GSTP1) OTLP0A0Y GSTP1_HUMAN Decreases Activity [22]
Nuclear protein 1 (NUPR1) OT4FU8C0 NUPR1_HUMAN Increases Expression [11]
Alpha-1-antichymotrypsin (SERPINA3) OT9BP2S0 AACT_HUMAN Increases Expression [11]
Serine protease hepsin (HPN) OT7QNA61 HEPS_HUMAN Increases Expression [11]
Fatty acid-binding protein, liver (FABP1) OTR34ETM FABPL_HUMAN Increases Expression [11]
Asparagine synthetase (ASNS) OT8R922G ASNS_HUMAN Increases Expression [11]
Solute carrier family 2, facilitated glucose transporter member 3 (SLC2A3) OT2HZK5M GTR3_HUMAN Decreases Expression [11]
Lanosterol synthase (LSS) OT9W2SFH LSS_HUMAN Increases Expression [11]
Inhibin beta E chain (INHBE) OTOI2NYG INHBE_HUMAN Increases Expression [11]
Transgelin (TAGLN) OTAEZ0KP TAGL_HUMAN Decreases Expression [11]
Acid ceramidase (ASAH1) OT1DNGXL ASAH1_HUMAN Increases Expression [11]
Nuclear receptor subfamily 0 group B member 2 (NR0B2) OT7UVICX NR0B2_HUMAN Increases Expression [11]
Lysophospholipase D GDPD3 (GDPD3) OTOHM9QM GDPD3_HUMAN Increases Expression [11]
Fibronectin type III domain-containing protein 4 (FNDC4) OTOQK0WK FNDC4_HUMAN Increases Expression [11]
Protein DEPP1 (DEPP1) OTB36PHJ DEPP1_HUMAN Increases Expression [11]
Acetylcholinesterase (ACHE) OT2H8HG6 ACES_HUMAN Decreases Activity [23]
Stearoyl-CoA desaturase (SCD) OTB1073G SCD_HUMAN Increases Expression [24]
Transmembrane protease serine 2 (TMPRSS2) OTN44YQ5 TMPS2_HUMAN Increases Expression [25]
Albumin (ALB) OTVMM513 ALBU_HUMAN Affects Binding [26]
Beta-2 adrenergic receptor (ADRB2) OTSDOX4Q ADRB2_HUMAN Decreases Expression [27]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [28]
Alpha-1-acid glycoprotein 2 (ORM2) OTRJGZP8 A1AG2_HUMAN Affects Binding [29]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [30]
Caspase-7 (CASP7) OTAPJ040 CASP7_HUMAN Increases Activity [30]
Heat shock factor protein 1 (HSF1) OTYNJ4KP HSF1_HUMAN Decreases Activity [31]
Hydroxymethylglutaryl-CoA synthase, cytoplasmic (HMGCS1) OTCO26FV HMCS1_HUMAN Increases Expression [24]
Glutamate receptor ionotropic, NMDA 1 (GRIN1) OTZ5YBO8 NMDZ1_HUMAN Decreases Expression [32]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [33]
Multidrug and toxin extrusion protein 1 (SLC47A1) OTZX0U5Q S47A1_HUMAN Decreases Activity [34]
Angiotensin-converting enzyme 2 (ACE2) OTTRZGU7 ACE2_HUMAN Decreases Expression [25]
DnaJ homolog subfamily C member 5 (DNAJC5) OTCZDXAL DNJC5_HUMAN Increases Expression [35]
SH3 and multiple ankyrin repeat domains protein 2 (SHANK2) OTSQTPFQ SHAN2_HUMAN Decreases Expression [32]
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⏷ Show the Full List of 32 DOT(s)

References

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2 Diazoxide 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: 2409).
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 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
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16 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.
17 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.
18 QTc prolongation associated with combination therapy of levofloxacin, imipramine, and fluoxetine. Ann Pharmacother. 2005 Mar;39(3):543-6.
19 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.
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22 Glutathione S-transferase pi as a target for tricyclic antidepressants in human brain. Acta Biochim Pol. 2004;51(1):207-12.
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24 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.
25 Effect of common medications on the expression of SARS-CoV-2 entry receptors in liver tissue. Arch Toxicol. 2020 Dec;94(12):4037-4041. doi: 10.1007/s00204-020-02869-1. Epub 2020 Aug 17.
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28 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.
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