General Information of Drug Combination (ID: DCZD8LK)

Drug Combination Name
PFK-158 Imipramine
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs PFK-158   DMIR21F Imipramine   DM2NUH3
N.A. 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: 2.41
Bliss Independence Score: 2.41
Loewe Additivity Score: 17.65
LHighest Single Agent (HSA) Score: 17.66

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of PFK-158
Disease Entry ICD 11 Status REF
Solid tumour/cancer 2A00-2F9Z Phase 1 [2]
PFK-158 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Renal carcinoma antigen NY-REN-56 (PFKFB3) TTTHMQJ F263_HUMAN Inhibitor [5]
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Indication(s) of Imipramine
Disease Entry ICD 11 Status REF
Depression 6A70-6A7Z Approved [3]
Nocturia MF55 Approved [4]
Imipramine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Norepinephrine transporter (NET) TTAWNKZ SC6A2_HUMAN Inhibitor [8]
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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 [9]
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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 [10]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [11]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Metabolism [12]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [13]
Cytochrome P450 3A7 (CYP3A7) DERD86B CP3A7_HUMAN Metabolism [14]
Cytochrome P450 2C18 (CYP2C18) DEZMWRE CP2CI_HUMAN Metabolism [11]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Metabolism [11]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [15]
Docosahexaenoic acid omega-hydroxylase (CYP4F11) DEIZLTN CP4FB_HUMAN Metabolism [16]
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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 [17]
Nuclear protein 1 (NUPR1) OT4FU8C0 NUPR1_HUMAN Increases Expression [6]
Alpha-1-antichymotrypsin (SERPINA3) OT9BP2S0 AACT_HUMAN Increases Expression [6]
Serine protease hepsin (HPN) OT7QNA61 HEPS_HUMAN Increases Expression [6]
Fatty acid-binding protein, liver (FABP1) OTR34ETM FABPL_HUMAN Increases Expression [6]
Asparagine synthetase (ASNS) OT8R922G ASNS_HUMAN Increases Expression [6]
Solute carrier family 2, facilitated glucose transporter member 3 (SLC2A3) OT2HZK5M GTR3_HUMAN Decreases Expression [6]
Lanosterol synthase (LSS) OT9W2SFH LSS_HUMAN Increases Expression [6]
Inhibin beta E chain (INHBE) OTOI2NYG INHBE_HUMAN Increases Expression [6]
Transgelin (TAGLN) OTAEZ0KP TAGL_HUMAN Decreases Expression [6]
Acid ceramidase (ASAH1) OT1DNGXL ASAH1_HUMAN Increases Expression [6]
Nuclear receptor subfamily 0 group B member 2 (NR0B2) OT7UVICX NR0B2_HUMAN Increases Expression [6]
Lysophospholipase D GDPD3 (GDPD3) OTOHM9QM GDPD3_HUMAN Increases Expression [6]
Fibronectin type III domain-containing protein 4 (FNDC4) OTOQK0WK FNDC4_HUMAN Increases Expression [6]
Protein DEPP1 (DEPP1) OTB36PHJ DEPP1_HUMAN Increases Expression [6]
Acetylcholinesterase (ACHE) OT2H8HG6 ACES_HUMAN Decreases Activity [18]
Stearoyl-CoA desaturase (SCD) OTB1073G SCD_HUMAN Increases Expression [19]
Transmembrane protease serine 2 (TMPRSS2) OTN44YQ5 TMPS2_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]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [25]
Caspase-7 (CASP7) OTAPJ040 CASP7_HUMAN Increases Activity [25]
Heat shock factor protein 1 (HSF1) OTYNJ4KP HSF1_HUMAN Decreases Activity [26]
Hydroxymethylglutaryl-CoA synthase, cytoplasmic (HMGCS1) OTCO26FV HMCS1_HUMAN Increases Expression [19]
Glutamate receptor ionotropic, NMDA 1 (GRIN1) OTZ5YBO8 NMDZ1_HUMAN Decreases Expression [27]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [28]
Multidrug and toxin extrusion protein 1 (SLC47A1) OTZX0U5Q S47A1_HUMAN Decreases Activity [29]
Angiotensin-converting enzyme 2 (ACE2) OTTRZGU7 ACE2_HUMAN Decreases Expression [20]
DnaJ homolog subfamily C member 5 (DNAJC5) OTCZDXAL DNJC5_HUMAN Increases Expression [30]
SH3 and multiple ankyrin repeat domains protein 2 (SHANK2) OTSQTPFQ SHAN2_HUMAN Decreases Expression [27]
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⏷ Show the Full List of 32 DOT(s)

References

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2 ClinicalTrials.gov (NCT02044861) Phase 1 Safety Study of ACT-PFK-158, 2HCl in Patients With Advanced Solid Malignancies. U.S. National Institutes of Health.
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: 357).
4 Imipramine FDA Label
5 Discovery of a PFKFB3 inhibitor for phase I trial testing that synergizes with the B-Raf inhibitor vemurafenib. Cancer Metab. 2014; 2(Suppl 1): P14.
6 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.
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20 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.
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.
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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.
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26 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.
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