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

General Information of Drug (ID: DMV2DY3)

• Drug Name: CARIPORIDE Drug Info
• Synonyms: Cariporide mesylate; UNII-0543W2JFRZ; 159138-81-5; Cariporide mesylate [USAN]; CHEMBL462831; 0543W2JFRZ; Cariporide mesylate (USAN); Cariporide mesilate; N-(4-Isopropyl-3-methanesulfonyl-benzoyl)-guanidine; DSSTox_RID_82284; DSSTox_CID_27344; DSSTox_GSID_47344; SCHEMBL221094; DTXSID3047344; AC1L4343; Tox21_300231; NCGC00254230-01; CAS-159138-81-5; D03406; (4-isopropyl-3-methanesulfonyl-benzoyl) guanidine methanesulfonate; Benzamide, N-(aminoiminomethyl)-4-(1-methylethyl)-3-(methylsulfonyl)-, monomethanesulfonate

Indication

Disease Entry	ICD 11	Status	REF
Angina pectoris	BA40	Discontinued in Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 151172
  CAS Number: CAS 159138-80-4
  TTD Drug ID: DMV2DY3

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	[5]
ENIPORIDE	DME7OCX	Cardiac arrhythmias	BC9Z	Discontinued in Phase 2	[3]
HOE-694	DML0B97	Heart arrhythmia	BC65	Terminated	[6]
N-(3-Methanesulfonyl-4-methyl-benzoyl)-guanidine	DMSVQJP	Discovery agent	N.A.	Investigative	[6]
N-(4-Chloro-3-methanesulfonyl-benzoyl)-guanidine	DMFG6MU	Discovery agent	N.A.	Investigative	[6]
N-(4-Cyano-3-methanesulfonyl-benzoyl)-guanidine	DMGI9EA	Discovery agent	N.A.	Investigative	[6]
N-(4-Bromo-3-methanesulfonyl-benzoyl)-guanidine	DMC28SN	Discovery agent	N.A.	Investigative	[6]
N-(3-Methanesulfonyl-4-methoxy-benzoyl)-guanidine	DM0H8CK	Discovery agent	N.A.	Investigative	[6]
N-(5-Methanesulfonyl-2-methyl-benzoyl)-guanidine	DM91463	Discovery agent	N.A.	Investigative	[6]
N-[2-(1H-benzoimidazol-2-yl)-benzoyl]-guanidine	DMI9GQV	Discovery agent	N.A.	Investigative	[7]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[11]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[12]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[13]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[14]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[15]
Marinol	DM70IK5	Anorexia nervosa cachexia	6B80	Approved	[16]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[17]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[18]
Paclitaxel	DMLB81S	Breast carcinoma		Approved	[19]
Arsenic	DMTL2Y1	N. A.	N. A.	Approved	[20]

Drug(s) Targeting Sodium/hydrogen exchanger 3 (SLC9A3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tenapanor	DMCOZJY	Irritable bowel syndrome	DD91.0	Approved	[8]
AVE-0657	DMESMHU	Cheyne-stokes respiration	MD11.Y	Phase 2	[9]
AZD1772//RDX5791	DMX5SG7	Chronic kidney disease	GB61	Phase 2	[10]
ENIPORIDE	DME7OCX	Cardiac arrhythmias	BC9Z	Discontinued in Phase 2	[3]
HOE-694	DML0B97	Heart arrhythmia	BC65	Terminated	[6]
N-(3-Methanesulfonyl-4-methyl-benzoyl)-guanidine	DMSVQJP	Discovery agent	N.A.	Investigative	[6]
N-(4-Chloro-3-methanesulfonyl-benzoyl)-guanidine	DMFG6MU	Discovery agent	N.A.	Investigative	[6]
N-(4-Cyano-3-methanesulfonyl-benzoyl)-guanidine	DMGI9EA	Discovery agent	N.A.	Investigative	[6]
N-(4-Bromo-3-methanesulfonyl-benzoyl)-guanidine	DMC28SN	Discovery agent	N.A.	Investigative	[6]
N-(3-Methanesulfonyl-4-methoxy-benzoyl)-guanidine	DM0H8CK	Discovery agent	N.A.	Investigative	[6]

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]
Sodium/hydrogen exchanger 3 (SLC9A3)	TTFZVPO	SL9A3_HUMAN	Inhibitor	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Sodium/hydrogen exchanger 1 (SLC9A1)	OT6HNHFV	SL9A1_HUMAN	Gene/Protein Processing	[4]

References

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• [2] Synthesis and bioactivity of substituted indan-1-ylideneaminoguanidine derivatives. Eur J Med Chem. 2009 Sep;44(9):3771-6.
• [3] Bicyclic acylguanidine Na+/H+ antiporter inhibitors. J Med Chem. 1998 Sep 10;41(19):3736-47.
• [4] Zoniporide: a potent and highly selective inhibitor of human Na(+)/H(+) exchanger-1. Eur J Pharmacol. 2002 Sep 6;451(1):37-41. doi: 10.1016/s0014-2999(02)02193-3.
• [5] 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.
• [6] (2-Methyl-5-(methylsulfonyl)benzoyl)guanidine Na+/H+ antiporter inhibitors. J Med Chem. 1997 Jun 20;40(13):2017-34.
• [7] Benzimidazol-2-yl or benzimidazol-2-ylthiomethyl benzoylguanidines as novel Na+/H+ exchanger inhibitors, synthesis and protection against ischemic-... Bioorg Med Chem Lett. 2007 May 1;17(9):2430-3.
• [8] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [9] Inhibition of central Na(+)/H(+) exchanger type 3 can alleviate sleep apnea in Sprague-Dawley rats. Chin Med J (Engl). 2014;127(1):48-53.
• [10] RDX5791, a First-in-Class Minimally Systemic NHE3 Inhibitor in Clinical Development for CIC and IBS-C, Increases Intestinal Sodium Leading to Enhanced Intestinal Fluid Volume and Transit. Gastroenterology. 2011;140(suppl 1):S99.
• [11] Multifaceted preventive effects of single agent quercetin on a human prostate adenocarcinoma cell line (PC-3): implications for nutritional transcriptomics and multi-target therapy. Med Oncol. 2011 Dec;28(4):1395-404. doi: 10.1007/s12032-010-9603-3. Epub 2010 Jul 2.
• [12] Troglitazone acts on cellular pH and DNA synthesis through a peroxisome proliferator-activated receptor gamma-independent mechanism in breast cancer-derived cell lines. Clin Cancer Res. 2004 Oct 15;10(20):7022-30. doi: 10.1158/1078-0432.CCR-04-0879.
• [13] 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.
• [14] Differential gene expression in human hepatocyte cell lines exposed to the antiretroviral agent zidovudine. Arch Toxicol. 2014 Mar;88(3):609-23. doi: 10.1007/s00204-013-1169-3. Epub 2013 Nov 30.
• [15] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [16] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [17] 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.
• [18] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [19] Paclitaxel induces apoptosis via protein kinase A- and p38 mitogen-activated protein-dependent inhibition of the Na+/H+ exchanger (NHE) NHE isoform 1 in human breast cancer cells. Clin Cancer Res. 2003 Jun;9(6):2366-73.
• [20] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.