General Information of Drug Combination (ID: DCFPZ84)

Drug Combination Name
Trihexyphenidyl Fibrates
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Trihexyphenidyl   DMB19L8 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: 15.14
Bliss Independence Score: 15.14
Loewe Additivity Score: 28.44
LHighest Single Agent (HSA) Score: 28.45

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Trihexyphenidyl
Disease Entry ICD 11 Status REF
Dystonia 8A02 Approved [2]
Parkinson disease 8A00.0 Approved [2]
Parkinsonian disorder N.A. Approved [3]
Postencephalitic Parkinson disease N.A. Approved [3]
Obesity 5B81 Investigative [4]
Trihexyphenidyl Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Muscarinic acetylcholine receptor M1 (CHRM1) TTZ9SOR ACM1_HUMAN Antagonist [6]
Adrenergic receptor beta-3 (ADRB3) TTMXGCW ADRB3_HUMAN Agonist [4]
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Trihexyphenidyl Interacts with 13 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Proepiregulin (EREG) OTRM4NQY EREG_HUMAN Increases Expression [7]
Interleukin-1 alpha (IL1A) OTPSGILV IL1A_HUMAN Increases Expression [7]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Increases Expression [7]
Antileukoproteinase (SLPI) OTUNFUU8 SLPI_HUMAN Increases Expression [7]
Hepatocyte growth factor receptor (MET) OT7K55MU MET_HUMAN Increases Expression [7]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [7]
Bone morphogenetic protein 6 (BMP6) OT9WN536 BMP6_HUMAN Increases Expression [7]
Prostaglandin G/H synthase 2 (PTGS2) OT75U9M4 PGH2_HUMAN Increases Expression [7]
Tumor necrosis factor-inducible gene 6 protein (TNFAIP6) OT1SLUZH TSG6_HUMAN Increases Expression [7]
Interleukin-24 (IL24) OT4VUWH1 IL24_HUMAN Increases Expression [7]
PTB-containing, cubilin and LRP1-interacting protein (PID1) OT5YJ7FI PCLI1_HUMAN Increases Expression [7]
Cystine/glutamate transporter (SLC7A11) OTKJ6PXW XCT_HUMAN Increases Expression [7]
Apolipoprotein E (APOE) OTFOWL2H APOE_HUMAN Increases Response To Substance [8]
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⏷ Show the Full List of 13 DOT(s)
Indication(s) of Fibrates
Disease Entry ICD 11 Status REF
Dyslipidemia 5C80-5C81 Investigative [5]
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 [5]
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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 [13]
Cytochrome P450 2A6 (CYP2A6) OT52TWG3 CP2A6_HUMAN Decreases Expression [14]
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases Expression [9]
Cytochrome P450 2C8 (CYP2C8) OTHCWT42 CP2C8_HUMAN Increases Expression [9]
Cytochrome P450 2C9 (CYP2C9) OTGLBN29 CP2C9_HUMAN Increases Expression [15]
Plasminogen activator inhibitor 1 (SERPINE1) OTT0MPQ3 PAI1_HUMAN Increases Expression [16]
Retinol-binding protein 1 (RBP1) OTRP1MFC RET1_HUMAN Decreases Expression [17]
Peroxisome proliferator-activated receptor gamma (PPARG) OTHMARHO PPARG_HUMAN Affects Binding [13]
Stromal cell-derived factor 1 (CXCL12) OT2QX5LL SDF1_HUMAN Decreases Expression [17]
Carnitine O-palmitoyltransferase 1, liver isoform (CPT1A) OTI862QH CPT1A_HUMAN Increases Expression [17]
Peroxisome proliferator-activated receptor delta (PPARD) OTI4WTOP PPARD_HUMAN Affects Binding [13]
Perilipin-2 (PLIN2) OTRXJ9UN PLIN2_HUMAN Increases Expression [17]
Angiopoietin-related protein 4 (ANGPTL4) OTQL5SPX ANGL4_HUMAN Increases Expression [17]
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⏷ Show the Full List of 13 DOT(s)

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 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: 7315).
3 Trihexyphenidyl FDA Label
4 Obesity: pathophysiology and clinical management. Curr Med Chem. 2009;16(4):506-21.
5 Emerging antidyslipidemic drugs. Expert Opin Emerg Drugs. 2008 Jun;13(2):363-81.
6 The role of M1 muscarinic cholinergic receptors in the discriminative stimulus properties of N-desmethylclozapine and the atypical antipsychotic dr... Psychopharmacology (Berl). 2009 Apr;203(2):295-301.
7 An in vitro coculture system of human peripheral blood mononuclear cells with hepatocellular carcinoma-derived cells for predicting drug-induced liver injury. Arch Toxicol. 2021 Jan;95(1):149-168. doi: 10.1007/s00204-020-02882-4. Epub 2020 Aug 20.
8 Increased mental slowing associated with the APOE epsilon4 allele after trihexyphenidyl oral anticholinergic challenge in healthy elderly. Am J Geriatr Psychiatry. 2008 Feb;16(2):116-24. doi: 10.1097/JGP.0b013e31815aff75.
9 Comparative effects of fibrates on drug metabolizing enzymes in human hepatocytes. Pharm Res. 2005 Jan;22(1):71-8.
10 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.
11 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.
12 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.
13 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.
14 CYP2A5/CYP2A6 expression in mouse and human hepatocytes treated with various in vivo inducers. Drug Metab Dispos. 2000 Nov;28(11):1321-6.
15 Expression and induction potential of cytochromes P450 in human cryopreserved hepatocytes. Drug Metab Dispos. 2005 Jul;33(7):1004-16.
16 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.
17 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.