General Information of Drug Combination (ID: DC8ICTI)

Drug Combination Name
Trihexyphenidyl Amiloride
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Trihexyphenidyl   DMB19L8 Amiloride   DMRTSGP
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: 8.27
Bliss Independence Score: 8.27
Loewe Additivity Score: 22.06
LHighest Single Agent (HSA) Score: 22.07

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 [7]
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 [8]
Interleukin-1 alpha (IL1A) OTPSGILV IL1A_HUMAN Increases Expression [8]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Increases Expression [8]
Antileukoproteinase (SLPI) OTUNFUU8 SLPI_HUMAN Increases Expression [8]
Hepatocyte growth factor receptor (MET) OT7K55MU MET_HUMAN Increases Expression [8]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [8]
Bone morphogenetic protein 6 (BMP6) OT9WN536 BMP6_HUMAN Increases Expression [8]
Prostaglandin G/H synthase 2 (PTGS2) OT75U9M4 PGH2_HUMAN Increases Expression [8]
Tumor necrosis factor-inducible gene 6 protein (TNFAIP6) OT1SLUZH TSG6_HUMAN Increases Expression [8]
Interleukin-24 (IL24) OT4VUWH1 IL24_HUMAN Increases Expression [8]
PTB-containing, cubilin and LRP1-interacting protein (PID1) OT5YJ7FI PCLI1_HUMAN Increases Expression [8]
Cystine/glutamate transporter (SLC7A11) OTKJ6PXW XCT_HUMAN Increases Expression [8]
Apolipoprotein E (APOE) OTFOWL2H APOE_HUMAN Increases Response To Substance [9]
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⏷ Show the Full List of 13 DOT(s)
Indication(s) of Amiloride
Disease Entry ICD 11 Status REF
Congestive heart failure BD10 Approved [5]
Edema MG29 Approved [6]
Amiloride Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Acid-sensing ion channel 1 (ASIC1) TTRJYB6 ASIC1_HUMAN Modulator [11]
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Amiloride Interacts with 2 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Organic cation transporter 2 (SLC22A2) DT9IDPW S22A2_HUMAN Substrate [12]
Organic cation transporter 1 (SLC22A1) DTT79CX S22A1_HUMAN Substrate [13]
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Amiloride Interacts with 15 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Diamine oxidase (AOC1) OTRC220K AOC1_HUMAN Decreases Activity [14]
3-phosphoinositide-dependent protein kinase 1 (PDPK1) OTT09ZVP PDPK1_HUMAN Decreases Phosphorylation [15]
Dysferlin (DYSF) OTNSKJU0 DYSF_HUMAN Decreases Expression [16]
Urokinase-type plasminogen activator (PLAU) OTX0QGKK UROK_HUMAN Decreases Activity [17]
Angiotensinogen (AGT) OTBZLYR3 ANGT_HUMAN Increases Expression [18]
Protein c-Fos (FOS) OTJBUVWS FOS_HUMAN Increases Expression [19]
Receptor tyrosine-protein kinase erbB-2 (ERBB2) OTOAUNCK ERBB2_HUMAN Decreases Phosphorylation [15]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Decreases Activity [20]
Myogenic factor 5 (MYF5) OTTVO2S5 MYF5_HUMAN Increases Expression [16]
G2/mitotic-specific cyclin-B1 (CCNB1) OT19S7E5 CCNB1_HUMAN Decreases Expression [21]
Pancreas/duodenum homeobox protein 1 (PDX1) OTX1DKRA PDX1_HUMAN Decreases Uptake [22]
Serine/threonine-protein phosphatase PP1-alpha catalytic subunit (PPP1CA) OT7Y43A1 PP1A_HUMAN Decreases Phosphorylation [15]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Decreases Activity [20]
Multidrug and toxin extrusion protein 1 (SLC47A1) OTZX0U5Q S47A1_HUMAN Decreases Activity [23]
Glutamate receptor-interacting protein 1 (GRIP1) OT958HK1 GRIP1_HUMAN Affects Response To Substance [24]
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⏷ Show the Full List of 15 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 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: 2421).
6 Amiloride FDA Label
7 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.
8 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.
9 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.
10 Reduction of intracellular pH inhibits the expression of VEGF in K562 cells after targeted inhibition of the Na+/H+ exchanger. Leuk Res. 2007 Apr;31(4):507-14. doi: 10.1016/j.leukres.2006.06.015. Epub 2006 Aug 1.
11 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
12 Characterization of regulatory mechanisms and states of human organic cation transporter 2. Am J Physiol Cell Physiol. 2006 Jun;290(6):C1521-31.
13 Identification of novel substrates and structure-activity relationship of cellular uptake mediated by human organic cation transporters 1 and 2. J Med Chem. 2013 Sep 26;56(18):7232-42.
14 Diamine oxidase is the amiloride-binding protein and is inhibited by amiloride analogues. J Biol Chem. 1994 Apr 1;269(13):9921-5.
15 Role of HER-2/neu signaling in sensitivity to tumor necrosis factor-related apoptosis-inducing ligand: enhancement of TRAIL-mediated apoptosis by amiloride. J Cell Biochem. 2005 Oct 1;96(2):376-89. doi: 10.1002/jcb.20512.
16 In vivo and in vitro dysferlin expression in human muscle satellite cells. J Neuropathol Exp Neurol. 2004 Oct;63(10):1104-13. doi: 10.1093/jnen/63.10.1104.
17 Amplification of urokinase gene in prostate cancer. Cancer Res. 2001 Jul 15;61(14):5340-4.
18 Amiloride, spironolactone, and potassium chloride in thiazide-treated hypertensive patients. Clin Pharmacol Ther. 1980 Apr;27(4):533-43. doi: 10.1038/clpt.1980.75.
19 Selection of drugs to test the specificity of the Tg.AC assay by screening for induction of the gadd153 promoter in vitro. Toxicol Sci. 2003 Aug;74(2):260-70. doi: 10.1093/toxsci/kfg113. Epub 2003 May 2.
20 Association of CYP1A1 and CYP1B1 inhibition in in vitro assays with drug-induced liver injury. J Toxicol Sci. 2021;46(4):167-176. doi: 10.2131/jts.46.167.
21 Reduction in the radiation-induced late S phase and G2 blocks in HL-60 cell populations by amiloride, an efficient inhibitor of the Na+/H+ transporter. Cancer Res. 1998 Feb 1;58(3):413-20.
22 PDX-1 protein is internalized by lipid raft-dependent macropinocytosis. Cell Transplant. 2005;14(9):637-45. doi: 10.3727/000000005783982648.
23 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.
24 Population-based in vitro hazard and concentration-response assessment of chemicals: the 1000 genomes high-throughput screening study. Environ Health Perspect. 2015 May;123(5):458-66. doi: 10.1289/ehp.1408775. Epub 2015 Jan 13.