General Information of Drug Combination (ID: DCNEG2E)

Drug Combination Name
Acitretin Amiloride
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Acitretin   DM8BKU9 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: 4.36
Bliss Independence Score: 4.36
Loewe Additivity Score: 13.69
LHighest Single Agent (HSA) Score: 13.69

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Acitretin
Disease Entry ICD 11 Status REF
Psoriasis vulgaris EA90 Approved [2]
Acitretin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Signal transducer and activator of transcription 3 (STAT3) TTH8FZW STAT3_HUMAN Inhibitor [5]
------------------------------------------------------------------------------------
Acitretin Interacts with 14 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Decreases Activity [6]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Activity [7]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [8]
Retinoic acid receptor RXR-alpha (RXRA) OTP1TBDM RXRA_HUMAN Affects Binding [9]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Decreases Expression [10]
Tumor necrosis factor receptor superfamily member 6 (FAS) OTP9XG86 TNR6_HUMAN Increases Expression [7]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Expression [10]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Expression [10]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [11]
Tumor necrosis factor ligand superfamily member 6 (FASLG) OTZARCHH TNFL6_HUMAN Increases Expression [7]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Activity [7]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [8]
FAS-associated death domain protein (FADD) OTV7GFHH FADD_HUMAN Increases Expression [7]
Caspase-8 (CASP8) OTA8TVI8 CASP8_HUMAN Increases Activity [7]
------------------------------------------------------------------------------------
⏷ Show the Full List of 14 DOT(s)
Indication(s) of Amiloride
Disease Entry ICD 11 Status REF
Congestive heart failure BD10 Approved [3]
Edema MG29 Approved [4]
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 [13]
------------------------------------------------------------------------------------
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 [14]
Organic cation transporter 1 (SLC22A1) DTT79CX S22A1_HUMAN Substrate [15]
------------------------------------------------------------------------------------
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 [16]
3-phosphoinositide-dependent protein kinase 1 (PDPK1) OTT09ZVP PDPK1_HUMAN Decreases Phosphorylation [17]
Dysferlin (DYSF) OTNSKJU0 DYSF_HUMAN Decreases Expression [18]
Urokinase-type plasminogen activator (PLAU) OTX0QGKK UROK_HUMAN Decreases Activity [19]
Angiotensinogen (AGT) OTBZLYR3 ANGT_HUMAN Increases Expression [20]
Protein c-Fos (FOS) OTJBUVWS FOS_HUMAN Increases Expression [21]
Receptor tyrosine-protein kinase erbB-2 (ERBB2) OTOAUNCK ERBB2_HUMAN Decreases Phosphorylation [17]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Decreases Activity [6]
Myogenic factor 5 (MYF5) OTTVO2S5 MYF5_HUMAN Increases Expression [18]
G2/mitotic-specific cyclin-B1 (CCNB1) OT19S7E5 CCNB1_HUMAN Decreases Expression [22]
Pancreas/duodenum homeobox protein 1 (PDX1) OTX1DKRA PDX1_HUMAN Decreases Uptake [23]
Serine/threonine-protein phosphatase PP1-alpha catalytic subunit (PPP1CA) OT7Y43A1 PP1A_HUMAN Decreases Phosphorylation [17]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Decreases Activity [6]
Multidrug and toxin extrusion protein 1 (SLC47A1) OTZX0U5Q S47A1_HUMAN Decreases Activity [24]
Glutamate receptor-interacting protein 1 (GRIP1) OT958HK1 GRIP1_HUMAN Affects Response To Substance [25]
------------------------------------------------------------------------------------
⏷ 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: 7598).
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: 2421).
4 Amiloride FDA Label
5 Effects of acitretin on the expression of signaling pathway-related genes in epidermal squamous-cell carcinoma cells. Zhonghua Zhong Liu Za Zhi. 2006 Jan;28(1):21-4.
6 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.
7 Acitretin induces apoptosis through CD95 signalling pathway in human cutaneous squamous cell carcinoma cell line SCL-1. J Cell Mol Med. 2009 Sep;13(9A):2888-98. doi: 10.1111/j.1582-4934.2008.00397.x. Epub 2009 Jun 20.
8 [Effects of all-trans-retinoic acid, acitretin and tazarotene on apoptosis and Bax/Bcl-2 expressions of human melanoma cells A375 and the significance]. Di Yi Jun Yi Da Xue Xue Bao. 2005 Aug;25(8):972-4, 978.
9 Limited Chemical Structural Diversity Found to Modulate Thyroid Hormone Receptor in the Tox21 Chemical Library. Environ Health Perspect. 2019 Sep;127(9):97009. doi: 10.1289/EHP5314. Epub 2019 Sep 30.
10 [Acitretin induces apoptosis and changes of relative signaling pathway in epidermoid carcinoma cell line A431]. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2006 Mar;35(2):182-8. doi: 10.3785/j.issn.1008-9292.2006.02.013.
11 Effects of ATRA, acitretin and tazarotene on growth and apoptosis of Tca8113 cells. J Huazhong Univ Sci Technolog Med Sci. 2005;25(4):393-6. doi: 10.1007/BF02828205.
12 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.
13 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
14 Characterization of regulatory mechanisms and states of human organic cation transporter 2. Am J Physiol Cell Physiol. 2006 Jun;290(6):C1521-31.
15 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.
16 Diamine oxidase is the amiloride-binding protein and is inhibited by amiloride analogues. J Biol Chem. 1994 Apr 1;269(13):9921-5.
17 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.
18 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.
19 Amplification of urokinase gene in prostate cancer. Cancer Res. 2001 Jul 15;61(14):5340-4.
20 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.
21 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.
22 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.
23 PDX-1 protein is internalized by lipid raft-dependent macropinocytosis. Cell Transplant. 2005;14(9):637-45. doi: 10.3727/000000005783982648.
24 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.
25 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.