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

General Information of Drug (ID: DMV5KR3)

• Drug Name: Ebrotidine Drug Info
• Synonyms: Ebrocit; FI-3542

Indication

Disease Entry	ICD 11	Status	REF
Duodenal ulcer	DA63	Withdrawn from market	[1]

• Cross-matching ID:
  PubChem CID: 65869
  ChEBI ID: CHEMBL135774
  CAS Number: CAS 100981-43-9
  TTD Drug ID: DMV5KR3

Molecule-Related Drug Atlas

Drug(s) Targeting Histamine H2 receptor (H2R)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ranitidine	DM0GUSX	Gastric ulcer	DA60	Approved	[4]
Cimetidine	DMH61ZB	Acid-reflux disorder	DA22	Approved	[5]
Famotidine	DMRL3AB	Gastric ulcer	DA60	Approved	[5]
Nizatidine	DMGFV3Z	Acid-reflux disorder	DA22	Approved	[6]
Betazole	DMUFGAY	Gastric secretory disorder	DD90	Approved	[7]
Pibutidine	DMXSTRM	Ulcerative colitis	DD71	Discontinued in Phase 3	[8]
Osutidine	DMN7TL8	Duodenal ulcer	DA63	Discontinued in Phase 3	[9]
KU-1257	DMZMFX6	Duodenal ulcer	DA63	Discontinued in Phase 3	[10]
Lavoltidine	DMTY5VE	Gastroesophageal reflux disease	DA22.Z	Discontinued in Phase 2	[11]
IGN-2098	DMU4N1O	Duodenal ulcer	DA63	Discontinued in Phase 2	[12]

Drug(s) Affected By Phosphatidylcholine translocator ABCB4 (ABCB4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Paclitaxel	DMLB81S	Breast carcinoma		Approved	[13]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[14]
Methysergide	DM1EF73	Migraine	8A80	Approved	[3]
Clavulanate	DM2FGRT	Bacteremia	1A73	Approved	[15]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[16]
Lapatinib	DM3BH1Y	Breast cancer	2C60-2C65	Approved	[3]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[17]
obeticholic acid	DM3Q1SM	Primary biliary cholangitis	DB96.1	Approved	[18]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[19]
Omeprazole	DM471KJ	Cystic fibrosis	CA25	Approved	[20]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Histamine H2 receptor (H2R)	TTQHJ1K	HRH2_HUMAN	Modulator	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Phosphatidylcholine translocator ABCB4 (ABCB4)	OTE6PY83	MDR3_HUMAN	Gene/Protein Processing	[3]

References

• [1] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001139)
• [2] Histamine H2-receptor antagonist action of ebrotidine. Effects on gastric acid secretion, gastrin levels and NSAID-induced gastrotoxicity in the rat. Arzneimittelforschung. 1997 Apr;47(4A):439-46.
• [3] Evaluating the Role of Multidrug Resistance Protein 3 (MDR3) Inhibition in Predicting Drug-Induced Liver Injury Using 125 Pharmaceuticals. Chem Res Toxicol. 2017 May 15;30(5):1219-1229. doi: 10.1021/acs.chemrestox.7b00048. Epub 2017 May 4.
• [4] Knockouts model the 100 best-selling drugs--will they model the next 100 Nat Rev Drug Discov. 2003 Jan;2(1):38-51.
• [5] Histamine H1 and H2 receptor antagonists accelerate skin barrier repair and prevent epidermal hyperplasia induced by barrier disruption in a dry environment. J Invest Dermatol. 2001 Feb;116(2):261-5.
• [6] Does the use of nizatidine, as a pro-kinetic agent, improve gastric emptying in patients post-oesophagectomy J Gastrointest Surg. 2009 Mar;13(3):432-7.
• [7] Effect of nizatidine and cimetidine on betazole-stimulated gastric secretion of normal subjects: comparison of effects on acid, water, and pepsin. Am J Gastroenterol. 1988 Jan;83(1):32-6.
• [8] Comparative pharmacology of epibatidine: a potent agonist for neuronal nicotinic acetylcholine receptors. Mol Pharmacol. 1995 Oct;48(4):774-82.
• [9] Effects of osutidine (T-593) and its enantiomers on gastric mucosal hemodynamics and mucosal integrity in anesthetized rats. Arzneimittelforschung. 2001 Jan;51(1):46-50.
• [10] Pharmacological profiles of the new histamine H2-receptor antagonist N-ethyl-N'-[3-[3-(piperidinomethyl)phenoxy] propyl] urea. Arzneimittelforschung. 1993 Feb;43(2):129-33.
• [11] New and Future Drug Development for Gastroesophageal Reflux Disease. J Neurogastroenterol Motil. 2014 January; 20(1): 6-16.
• [12] Effects of IGN-2098, a new histamine H2-receptor antagonist, on gastric secretion and gastric and duodenal lesions induced in rats. Comparison with roxatidine. Nihon Yakurigaku Zasshi. 1992 Mar;99(3):167-80.
• [13] [Reversal effect of MDR1 and MDR3 gene silencing on resistance of A2780/taxol cells to paclitaxel]. Zhonghua Fu Chan Ke Za Zhi. 2007 Jun;42(6):412-6.
• [14] 8-Methoxypsoralen disrupts MDR3-mediated phospholipids efflux and bile acid homeostasis and its relevance to hepatotoxicity. Toxicology. 2017 Jul 1;386:40-48. doi: 10.1016/j.tox.2017.05.011. Epub 2017 May 24.
• [15] Molecular mechanisms of hepatotoxic cholestasis by clavulanic acid: Role of NRF2 and FXR pathways. Food Chem Toxicol. 2021 Dec;158:112664. doi: 10.1016/j.fct.2021.112664. Epub 2021 Nov 9.
• [16] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [17] 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.
• [18] Pharmacotoxicology of clinically-relevant concentrations of obeticholic acid in an organotypic human hepatocyte system. Toxicol In Vitro. 2017 Mar;39:93-103.
• [19] Species-specific toxicity of diclofenac and troglitazone in primary human and rat hepatocytes. Chem Biol Interact. 2009 Apr 15;179(1):17-24.
• [20] Evaluation of gene induction of drug-metabolizing enzymes and transporters in primary culture of human hepatocytes using high-sensitivity real-time reverse transcription PCR. Yakugaku Zasshi. 2002 May;122(5):339-61.