Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DM3TPMO)

• Drug Name: 5'-(N-ethyl-N-isopropyl)amiloride Drug Info
• Synonyms: EIPA; 5-(N-Ethyl-N-isopropyl)amiloride; 1154-25-2; Ethylisopropylamiloride; 5-(Ethylisopropyl)amiloride; Ethyl isopropyl amiloride; 5-(N-ethyl-N-isopropyl)-Amiloride; 3-Amino-N-(aminoiminomethyl)-6-chloro-5-[ethyl(1-methylethyl)amino]-2-pyrazinecarboxamide; N-Amidino-3-amino-5-ethylisopropylamino-6-chloropyrazine carboxamide; C11H18ClN7O; CHEMBL517986; 5-(N-Ethyl-N-isopropyl) Amiloride; 3-Amino-N-(aminoiminomethyl)-6-chloro-5-(ethyl(1-methylethyl)amino)pyrazinecarboxamide

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 1795
  ChEBI ID: CHEMBL517986
  CAS Number: CAS 1154-25-2
  TTD Drug ID: DM3TPMO
  VARIDT Drug ID: DR00893

Molecule-Related Drug Atlas

Drug(s) Targeting Sodium/hydrogen exchanger 1 (SLC9A1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Zoniporide hydrochloride	DM8L7JD	Angina pectoris	BA40	Phase 3	[7]
CARIPORIDE	DMV2DY3	Angina pectoris	BA40	Discontinued in Phase 2	[8]
ENIPORIDE	DME7OCX	Cardiac arrhythmias	BC9Z	Discontinued in Phase 2	[9]
HOE-694	DML0B97	Heart arrhythmia	BC65	Terminated	[10]
N-(3-Methanesulfonyl-4-methyl-benzoyl)-guanidine	DMSVQJP	Discovery agent	N.A.	Investigative	[10]
N-(4-Chloro-3-methanesulfonyl-benzoyl)-guanidine	DMFG6MU	Discovery agent	N.A.	Investigative	[10]
N-(4-Cyano-3-methanesulfonyl-benzoyl)-guanidine	DMGI9EA	Discovery agent	N.A.	Investigative	[10]
N-(4-Bromo-3-methanesulfonyl-benzoyl)-guanidine	DMC28SN	Discovery agent	N.A.	Investigative	[10]
N-(3-Methanesulfonyl-4-methoxy-benzoyl)-guanidine	DM0H8CK	Discovery agent	N.A.	Investigative	[10]
N-(5-Methanesulfonyl-2-methyl-benzoyl)-guanidine	DM91463	Discovery agent	N.A.	Investigative	[10]

Drug(s) Affected By Albumin (ALB)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[11]
Sulfamethoxazole	DMB08GE	Acute otitis media	AB00	Approved	[12]
Tolbutamide	DM02AWV	Advanced cancer	2A00-2F9Z	Approved	[13]
Diazepam	DM08E9O	Alcohol withdrawal		Approved	[14]
Sertraline	DM0FB1J	Coronary heart disease	BA80.Z	Approved	[15]
Methimazole	DM25FL8	Hyperthyroidism	5A02	Approved	[16]
Imipramine	DM2NUH3	Depression	6A70-6A7Z	Approved	[17]
Colchicine	DM2POTE	Acute gout flare	FA25.0	Approved	[18]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[19]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[20]

Drug(s) Affected By Fumarylacetoacetase (FAH)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Quercetin	DM3NC4M	Obesity	5B81	Approved	[21]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[22]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[23]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[24]
Ivermectin	DMDBX5F	Intestinal strongyloidiasis due to nematode parasite	1F6B	Approved	[25]
Fenofibrate	DMFKXDY	Coronary atherosclerosis		Approved	[26]
Mifepristone	DMGZQEF	Cushing disease	5A70	Approved	[27]
Temozolomide	DMKECZD	Adenocarcinoma	2D40	Approved	[28]
Sodium lauryl sulfate	DMLJ634	Constipation	DD91.1	Approved	[29]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[30]

Drug(s) Affected By Serine/arginine-rich splicing factor 3 (SRSF3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[31]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[32]
Marinol	DM70IK5	Anorexia nervosa cachexia	6B80	Approved	[33]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[34]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[24]
Ivermectin	DMDBX5F	Intestinal strongyloidiasis due to nematode parasite	1F6B	Approved	[25]
Cupric Sulfate	DMP0NFQ	Fungal infection	1F29-1F2F	Approved	[35]
Piroxicam	DMTK234	Osteoarthritis	FA00-FA05	Approved	[36]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[11]
Tamibarotene	DM3G74J	T-cell leukaemia	2A90	Phase 3	[32]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Sodium/hydrogen exchanger 1 (SLC9A1)	TTGSEFH	SL9A1_HUMAN	Inhibitor	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Protein Interaction/Cellular Processes	[3]
Fumarylacetoacetase (FAH)	OTGZA1YR	FAAA_HUMAN	Gene/Protein Processing	[4]
Serine/arginine-rich splicing factor 3 (SRSF3)	OTOFT707	SRSF3_HUMAN	Gene/Protein Processing	[5]
Vascular endothelial growth factor A, long form	OTIM9MZ3	VEGFA_HUMAN	Gene/Protein Processing	[6]

References

• [1] 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: 4186).
• [2] NHE1 inhibition by amiloride- and benzoylguanidine-type compounds. Inhibitor binding loci deduced from chimeras of NHE1 homologues with endogenous ... J Biol Chem. 2007 Jul 6;282(27):19716-27.
• [3] Chronic high glucose inhibits albumin reabsorption by lysosomal alkalinization in cultured porcine proximal tubular epithelial cells (LLC-PK1). Diabetes Res Clin Pract. 2006 Jun;72(3):223-30. doi: 10.1016/j.diabres.2005.10.019. Epub 2005 Nov 28.
• [4] Functional analysis and in vitro correction of splicing FAH mutations causing tyrosinemia type I. Clin Genet. 2014 Aug;86(2):167-71. doi: 10.1111/cge.12243. Epub 2013 Aug 21.
• [5] 5-(N-ethyl-N-isopropyl)-amiloride enhances SMN2 exon 7 inclusion and protein expression in spinal muscular atrophy cells. Ann Neurol. 2008 Jan;63(1):26-34. doi: 10.1002/ana.21241.
• [6] 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.
• [7] Zoniporde: a potent and selective inhibitor of the human sodium-hydrogen exchanger isoform 1 (NHE-1). Cardiovasc Drug Rev. 2003 Spring;21(1):17-32.
• [8] Synthesis and bioactivity of substituted indan-1-ylideneaminoguanidine derivatives. Eur J Med Chem. 2009 Sep;44(9):3771-6.
• [9] Bicyclic acylguanidine Na+/H+ antiporter inhibitors. J Med Chem. 1998 Sep 10;41(19):3736-47.
• [10] (2-Methyl-5-(methylsulfonyl)benzoyl)guanidine Na+/H+ antiporter inhibitors. J Med Chem. 1997 Jun 20;40(13):2017-34.
• [11] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [12] 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.
• [13] A protein-coated magnetic beads as a tool for the rapid drug-protein binding study. J Pharm Biomed Anal. 2010 Jul 8;52(3):420-4. doi: 10.1016/j.jpba.2009.06.023. Epub 2009 Jun 18.
• [14] The three recombinant domains of human serum albumin. Structural characterization and ligand binding properties. J Biol Chem. 1999 Oct 8;274(41):29303-10. doi: 10.1074/jbc.274.41.29303.
• [15] Exploring binding properties of sertraline with human serum albumin: Combination of spectroscopic and molecular modeling studies. Chem Biol Interact. 2015 Dec 5;242:235-46. doi: 10.1016/j.cbi.2015.10.006. Epub 2015 Oct 22.
• [16] Low-expressional IGF1 mediated methimazole-induced liver developmental toxicity in fetal mice. Toxicology. 2018 Sep 1;408:70-79. doi: 10.1016/j.tox.2018.07.004. Epub 2018 Jul 7.
• [17] 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.
• [18] [Colchicine in chronic liver disease of alcoholic etiology. Double-blind, randomized study of its effects on blood levels of plasma proteins and clinical course in patients]. Rev Assoc Med Bras (1992). 1995 May-Jun;41(3):207-12.
• [19] Editor's Highlight: Modeling Compound-Induced Fibrogenesis In Vitro Using Three-Dimensional Bioprinted Human Liver Tissues. Toxicol Sci. 2016 Dec;154(2):354-367. doi: 10.1093/toxsci/kfw169. Epub 2016 Sep 7.
• [20] Covalent binding of the flavonoid quercetin to human serum albumin. J Agric Food Chem. 2005 May 18;53(10):4194-7. doi: 10.1021/jf050061m.
• [21] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [22] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [23] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [24] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [25] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [26] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [27] Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium. Mol Hum Reprod. 2007 Sep;13(9):641-54.
• [28] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [29] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [30] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [31] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [32] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [33] JunD is involved in the antiproliferative effect of Delta9-tetrahydrocannabinol on human breast cancer cells. Oncogene. 2008 Aug 28;27(37):5033-44.
• [34] Cyclosporine A--induced oxidative stress in human renal mesangial cells: a role for ERK 1/2 MAPK signaling. Toxicol Sci. 2012 Mar;126(1):101-13.
• [35] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [36] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.