General Information of Drug Combination (ID: DCUY29R)

Drug Combination Name
Trifluoperazine Fibrates
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Trifluoperazine   DMKBYWI Fibrates   DMFNTMY
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: 7.27
Bliss Independence Score: 7.27
Loewe Additivity Score: 20.09
LHighest Single Agent (HSA) Score: 20.09

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Trifluoperazine
Disease Entry ICD 11 Status REF
Anxiety N.A. Approved [2]
Schizophrenia 6A20 Approved [3]
Trifluoperazine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Calmodulin (CALM) TTV3NH6 CALM1_HUMAN; CALM2_HUMAN; CALM3_HUMAN Inhibitor [6]
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Trifluoperazine Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [7]
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Trifluoperazine Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [8]
Dimethylaniline oxidase 2 (FMO2) DEIASEZ FMO2_HUMAN Metabolism [9]
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Trifluoperazine Interacts with 12 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Flavin-containing monooxygenase 2 (FMO2) OTUJUL9S FMO2_HUMAN Increases Oxidation [9]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Activity [10]
E3 ubiquitin-protein ligase parkin (PRKN) OTJBN41W PRKN_HUMAN Affects Localization [11]
Prolactin (PRL) OTWFQGX7 PRL_HUMAN Increases Expression [12]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [13]
Serine/threonine-protein kinase mTOR (MTOR) OTHH8KU7 MTOR_HUMAN Decreases Phosphorylation [14]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [13]
Hypoxia-inducible factor 1-alpha (HIF1A) OTADSC03 HIF1A_HUMAN Decreases Expression [15]
Stonin-2 (STON2) OT01JHHE STON2_HUMAN Decreases Expression [14]
D(3) dopamine receptor (DRD3) OT0OFFKB DRD3_HUMAN Increases ADR [16]
D(4) dopamine receptor (DRD4) OTAJTO7N DRD4_HUMAN Increases ADR [16]
D(2) dopamine receptor (DRD2) OTBLXKEG DRD2_HUMAN Increases ADR [16]
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⏷ Show the Full List of 12 DOT(s)
Indication(s) of Fibrates
Disease Entry ICD 11 Status REF
Dyslipidemia 5C80-5C81 Investigative [4]
Fibrates Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Peroxisome proliferator-activated receptor alpha (PPARA) TTJ584C PPARA_HUMAN Agonist [4]
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Fibrates Interacts with 13 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Peroxisome proliferator-activated receptor alpha (PPARA) OTK095PP PPARA_HUMAN Affects Binding [21]
Cytochrome P450 2A6 (CYP2A6) OT52TWG3 CP2A6_HUMAN Decreases Expression [22]
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases Expression [17]
Cytochrome P450 2C8 (CYP2C8) OTHCWT42 CP2C8_HUMAN Increases Expression [17]
Cytochrome P450 2C9 (CYP2C9) OTGLBN29 CP2C9_HUMAN Increases Expression [23]
Plasminogen activator inhibitor 1 (SERPINE1) OTT0MPQ3 PAI1_HUMAN Increases Expression [24]
Retinol-binding protein 1 (RBP1) OTRP1MFC RET1_HUMAN Decreases Expression [25]
Peroxisome proliferator-activated receptor gamma (PPARG) OTHMARHO PPARG_HUMAN Affects Binding [21]
Stromal cell-derived factor 1 (CXCL12) OT2QX5LL SDF1_HUMAN Decreases Expression [25]
Carnitine O-palmitoyltransferase 1, liver isoform (CPT1A) OTI862QH CPT1A_HUMAN Increases Expression [25]
Peroxisome proliferator-activated receptor delta (PPARD) OTI4WTOP PPARD_HUMAN Affects Binding [21]
Perilipin-2 (PLIN2) OTRXJ9UN PLIN2_HUMAN Increases Expression [25]
Angiopoietin-related protein 4 (ANGPTL4) OTQL5SPX ANGL4_HUMAN Increases Expression [25]
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⏷ Show the Full List of 13 DOT(s)

References

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2 Trifluoperazine FDA Label
3 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
4 Emerging antidyslipidemic drugs. Expert Opin Emerg Drugs. 2008 Jun;13(2):363-81.
5 Assessment of the inhibition potential of Licochalcone A against human UDP-glucuronosyltransferases. Food Chem Toxicol. 2016 Apr;90:112-22.
6 Inhibitory effect of jujuboside A on glutamate-mediated excitatory signal pathway in hippocampus. Planta Med. 2003 Aug;69(8):692-5.
7 Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
8 Psychotropic Medications Metabolized by Cytochromes P450 (CYP) 1A2 Enzyme and Relevant Drug Interactions: Review of Articles
9 Human FMO2-based microbial whole-cell catalysts for drug metabolite synthesis. Microb Cell Fact. 2015 Jun 12;14:82.
10 Characterization of the ATPase activity of the Mr 170,000 to 180,000 membrane glycoprotein (P-glycoprotein) associated with multidrug resistance in K562/ADM cells. Cancer Res. 1988 Sep 1;48(17):4926-32.
11 Rescue of Pink1 Deficiency by Stress-Dependent Activation of Autophagy. Cell Chem Biol. 2017 Apr 20;24(4):471-480.e4. doi: 10.1016/j.chembiol.2017.03.005. Epub 2017 Mar 30.
12 Association of high prolactin levels and neuroleptics immediately postpartum. J Neuropsychiatry Clin Neurosci. 1990 Winter;2(1):115. doi: 10.1176/jnp.2.1.115b.
13 Molecular mechanism of trifluoperazine induces apoptosis in human A549 lung adenocarcinoma cell lines. Mol Med Rep. 2009 Sep-Oct;2(5):811-7. doi: 10.3892/mmr_00000177.
14 Stonin 2 activates lysosomal-mTOR axis for cell survival in oral cancer. Toxicol In Vitro. 2023 Apr;88:105561. doi: 10.1016/j.tiv.2023.105561. Epub 2023 Jan 23.
15 Role of TRP channels and NCX in mediating hypoxia-induced [Ca(2+)](i) elevation in PC12 cells. Respir Physiol Neurobiol. 2008 Dec 31;164(3):386-93. doi: 10.1016/j.resp.2008.09.002. Epub 2008 Sep 7.
16 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.
17 Comparative effects of fibrates on drug metabolizing enzymes in human hepatocytes. Pharm Res. 2005 Jan;22(1):71-8.
18 Complementary deoxyribonucleic acid cloning and expression of a human liver uridine diphosphate-glucuronosyltransferase glucuronidating carboxylic acid-containing drugs. J Pharmacol Exp Ther. 1993 Jan;264(1):475-9.
19 Gastrointestinally distributed UDP-glucuronosyltransferase 1A10, which metabolizes estrogens and nonsteroidal anti-inflammatory drugs, depends upon phosphorylation. J Biol Chem. 2004 Jul 2;279(27):28320-9. doi: 10.1074/jbc.M401396200. Epub 2004 Apr 26.
20 Carboxylic acid drug-induced DNA nicking in HEK293 cells expressing human UDP-glucuronosyltransferases: role of acyl glucuronide metabolites and glycation pathways. Chem Res Toxicol. 2007 Oct;20(10):1520-7. doi: 10.1021/tx700188x. Epub 2007 Sep 20.
21 Fibrate and statin synergistically increase the transcriptional activities of PPARalpha/RXRalpha and decrease the transactivation of NFkappaB. Biochem Biophys Res Commun. 2002 Jan 11;290(1):131-9. doi: 10.1006/bbrc.2001.6141.
22 CYP2A5/CYP2A6 expression in mouse and human hepatocytes treated with various in vivo inducers. Drug Metab Dispos. 2000 Nov;28(11):1321-6.
23 Expression and induction potential of cytochromes P450 in human cryopreserved hepatocytes. Drug Metab Dispos. 2005 Jul;33(7):1004-16.
24 Effects of fibrate compounds on expression of plasminogen activator inhibitor-1 by cultured endothelial cells. Arterioscler Thromb Vasc Biol. 1999 Jun;19(6):1577-81. doi: 10.1161/01.atv.19.6.1577.
25 Decrease of hepatic stellate cells in rats with enhanced sensitivity to clofibrate-induced hepatocarcinogenesis. Cancer Sci. 2011 Apr;102(4):735-41. doi: 10.1111/j.1349-7006.2011.01856.x. Epub 2011 Feb 10.