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

General Information of Drug (ID: DMZ2VYG)

• Drug Name: burimamide Drug Info
• Synonyms: 1-[4-(1H-indazol-4-yl)butyl]-3-methylthiourea; AC1NSKDK; GTPL1229

Indication

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

• Cross-matching ID:
  PubChem CID: 3032915
  ChEBI ID: CHEBI:3221
  CAS Number: CAS 34970-69-9
  TTD Drug ID: DMZ2VYG

Molecule-Related Drug Atlas

Drug(s) Targeting Histamine H4 receptor (H4R)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PF-3893787	DMC2FAL	Atopic dermatitis	EA80	Phase 2	[5]
JNJ-38518168	DM9UMIO	Plaque psoriasis	EA90.0	Phase 2	[6]
UR-63325	DME6X27	Allergic rhinitis	CA08.0	Phase 2	[7]
Thioperamide	DM8S593	Cognitive impairment	6D71	Terminated	[8]
2-(2-(4-tert-Butylphenylthio)ethyl)-1H-imidazole	DMZVBPG	Discovery agent	N.A.	Investigative	[9]
impromidine	DMTDRPM	Discovery agent	N.A.	Investigative	[10]
Imetit	DMMJ6NS	Discovery agent	N.A.	Investigative	[11]
[125I]iodophenpropit	DMN4ABU	Discovery agent	N.A.	Investigative	[12]
(R)-alpha-methylhistamine	DMKAW4P	Discovery agent	N.A.	Investigative	[3]
N-[3H]alpha-methylhistamine	DMWDCV1	Discovery agent	N.A.	Investigative	[13]

Drug(s) Targeting Histamine H2 receptor (H2R)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ranitidine	DM0GUSX	Gastric ulcer	DA60	Approved	[14]
Cimetidine	DMH61ZB	Acid-reflux disorder	DA22	Approved	[15]
Famotidine	DMRL3AB	Gastric ulcer	DA60	Approved	[15]
Nizatidine	DMGFV3Z	Acid-reflux disorder	DA22	Approved	[16]
Betazole	DMUFGAY	Gastric secretory disorder	DD90	Approved	[17]
Ebrotidine	DMV5KR3	Duodenal ulcer	DA63	Withdrawn from market	[18]
Pibutidine	DMXSTRM	Ulcerative colitis	DD71	Discontinued in Phase 3	[19]
Osutidine	DMN7TL8	Duodenal ulcer	DA63	Discontinued in Phase 3	[20]
KU-1257	DMZMFX6	Duodenal ulcer	DA63	Discontinued in Phase 3	[21]
Lavoltidine	DMTY5VE	Gastroesophageal reflux disease	DA22.Z	Discontinued in Phase 2	[22]

Drug(s) Targeting Histamine H3 receptor (H3R)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Pitolisant	DM8RFNJ	Excessive daytime sleepiness	MG42	Approved	[23]
SUVN-G3031	DM3BO8G	Cognitive impairment	6D71	Phase 3	[24]
JNJ-17216498	DM1GRCU	Narcolepsy	7A20	Phase 2	[25]
GSK239512	DMBJMZC	Alzheimer disease	8A20	Phase 2	[26]
JNJ-39220675	DM0WY3H	Alcohol dependence	6C40.2	Phase 2	[27]
AZD-5213	DMOZ04X	Alzheimer disease	8A20	Phase 2	[28]
Bavisant	DM6CVZ5	Attention deficit hyperactivity disorder	6A05.Z	Phase 2	[29]
ABT-288	DM7X54F	Alzheimer disease	8A20	Phase 2	[30]
SAR-110894	DMCLEXM	Alzheimer disease	8A20	Phase 2	[28]
ABT-652	DMLEO2Z	Diabetic neuropathy	8C0Z	Phase 2	[31]

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	Agonist	[2]
Histamine H3 receptor (H3R)	TT9JNIC	HRH3_HUMAN	Antagonist	[3]
Histamine H4 receptor (H4R)	TTXJ178	HRH4_HUMAN	Antagonist	[4]

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: 1229).
• [2] Constitutive activity and structural instability of the wild-type human H2 receptor. J Neurochem. 1998 Aug;71(2):799-807.
• [3] Cloning and pharmacological characterization of a fourth histamine receptor (H(4)) expressed in bone marrow. Mol Pharmacol. 2001 Mar;59(3):420-6.
• [4] Comparison of human, mouse, rat, and guinea pig histamine H4 receptors reveals substantial pharmacological species variation. J Pharmacol Exp Ther. 2001 Oct;299(1):121-30.
• [5] Challenges of drug discovery in novel target space. The discovery and evaluation of PF-3893787: a novel histamine H4 receptor antagonist. Bioorg Med Chem Lett. 2011 Nov 1;21(21):6596-602.
• [6] The histamine H4 receptor: from orphan to the clinic. Front Pharmacol. 2015; 6: 65.
• [7] Azines as histamine H4 receptor antagonists. Front Biosci (Schol Ed). 2012 Jan 1;4:967-87.
• [8] Role of histamine in short- and long-term effects of methamphetamine on the developing mouse brain. J Neurochem. 2008 Nov;107(4):976-86.
• [9] Synthesis and structure-activity relationships of N-aryl-piperidine derivatives as potent (partial) agonists for human histamine H3 receptor. Bioorg Med Chem. 2010 Jul 15;18(14):5441-8.
• [10] Evaluation of histamine H1-, H2-, and H3-receptor ligands at the human histamine H4 receptor: identification of 4-methylhistamine as the first pote... J Pharmacol Exp Ther. 2005 Sep;314(3):1310-21.
• [11] Histamine excites neonatal rat sympathetic preganglionic neurons in vitro via activation of H1 receptors. J Neurophysiol. 2006 Apr;95(4):2492-500.
• [12] Discovery of novel human histamine H4 receptor ligands by large-scale structure-based virtual screening. J Med Chem. 2008 Jun 12;51(11):3145-53.
• [13] Histamine induces cytoskeletal changes in human eosinophils via the H(4) receptor. Br J Pharmacol. 2003 Nov;140(6):1117-27.
• [14] Knockouts model the 100 best-selling drugs--will they model the next 100 Nat Rev Drug Discov. 2003 Jan;2(1):38-51.
• [15] 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.
• [16] 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.
• [17] 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.
• [18] 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.
• [19] Comparative pharmacology of epibatidine: a potent agonist for neuronal nicotinic acetylcholine receptors. Mol Pharmacol. 1995 Oct;48(4):774-82.
• [20] 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.
• [21] 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.
• [22] New and Future Drug Development for Gastroesophageal Reflux Disease. J Neurogastroenterol Motil. 2014 January; 20(1): 6-16.
• [23] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [24] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [25] Acute wake-promoting actions of JNJ-5207852, a novel, diamine-based H3 antagonist. Br J Pharmacol. 2004 Nov;143(5):649-61.
• [26] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [27] JNJ-39220675, a novel selective histamine H3 receptor antagonist, reduces the abuse-related effects of alcohol in rats. Psychopharmacology (Berl). 2011 Apr;214(4):829-41.
• [28] SAR110894, a potent histamine H receptor antagonist, displays procognitive effects in rodents. Pharmacol Biochem Behav. 2012 Aug;102(2):203-14.
• [29] Randomized clinical study of a histamine H3 receptor antagonist for the treatment of adults with attention-deficit hyperactivity disorder. CNS Drugs. 2012 May 1;26(5):421-34.
• [30] A randomized study of H3 antagonist ABT-288 in mild-to-moderate Alzheimer's dementia.J Alzheimers Dis.2014;42(3):959-71.
• [31] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800032225)