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

General Information of Drug (ID: DM0CI4L)

• Drug Name: N-[3H]methylhistamine Drug Info
• Synonyms: 1-Methylhistamine; Tele-methylhistamine; 501-75-7; N1-Methylhistamine; N-Telle-methylhistamine; 2-(1-methyl-1H-imidazol-4-yl)ethanamine; 2-(1-methyl-1H-imidazol-4-yl)ethan-1-amine; 1-Methyl-1H-imidazole-4-ethanamine; 1H-Imidazole-4-ethanamine, 1-methyl-; 1-Methyl-4-histamine; UNII-KCB81T4EOF; N(sup 1)-Methylhistamine; NSC 66736; N-tele-Methylhistamine; CHEBI:29009; 1-methyl-4-(b-aminoethyl)imidazole; 1-Methyl-4-(2-aminoethyl)imidazole; KCB81T4EOF; 1-Methyl-4-(beta-aminoethyl)imidazole; BRN 0110757

Indication

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

• Cross-matching ID:
  PubChem CID: 3614
  ChEBI ID: CHEBI:29009
  CAS Number: CAS 501-75-7
  TTD Drug ID: DM0CI4L

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	[4]
JNJ-38518168	DM9UMIO	Plaque psoriasis	EA90.0	Phase 2	[5]
UR-63325	DME6X27	Allergic rhinitis	CA08.0	Phase 2	[6]
Thioperamide	DM8S593	Cognitive impairment	6D71	Terminated	[7]
2-(2-(4-tert-Butylphenylthio)ethyl)-1H-imidazole	DMZVBPG	Discovery agent	N.A.	Investigative	[8]
impromidine	DMTDRPM	Discovery agent	N.A.	Investigative	[9]
burimamide	DMZ2VYG	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	[2]

Drug(s) Targeting Histamine H3 receptor (H3R)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Pitolisant	DM8RFNJ	Excessive daytime sleepiness	MG42	Approved	[13]
SUVN-G3031	DM3BO8G	Cognitive impairment	6D71	Phase 3	[14]
JNJ-17216498	DM1GRCU	Narcolepsy	7A20	Phase 2	[15]
GSK239512	DMBJMZC	Alzheimer disease	8A20	Phase 2	[16]
JNJ-39220675	DM0WY3H	Alcohol dependence	6C40.2	Phase 2	[17]
AZD-5213	DMOZ04X	Alzheimer disease	8A20	Phase 2	[18]
Bavisant	DM6CVZ5	Attention deficit hyperactivity disorder	6A05.Z	Phase 2	[19]
ABT-288	DM7X54F	Alzheimer disease	8A20	Phase 2	[20]
SAR-110894	DMCLEXM	Alzheimer disease	8A20	Phase 2	[18]
ABT-652	DMLEO2Z	Diabetic neuropathy	8C0Z	Phase 2	[21]

Drug(s) Affected By Diamine oxidase (AOC1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[22]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[23]
Amiloride	DMRTSGP	Congestive heart failure	BD10	Approved	[24]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[25]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[26]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[27]
Aminoguanidine	DMJQDUC	Diabetic retinopathy	9B71.0	Phase 1	[24]
Benzo(a)pyrene	DMN7J43	N. A.	N. A.	Phase 1	[28]
PMID28870136-Compound-48	DMPIM9L	N. A.	N. A.	Patented	[29]
Putrescine	DMWE6V1	Burn and burn infection	ND90-NE2Z	Discontinued in Phase 2	[24]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Histamine H3 receptor (H3R)	TT9JNIC	HRH3_HUMAN	Agonist	[2]
Histamine H4 receptor (H4R)	TTXJ178	HRH4_HUMAN	Agonist	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Diamine oxidase (AOC1)	OTRC220K	AOC1_HUMAN	Regulation of Drug Effects	[3]

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: 1241).
• [2] Cloning and pharmacological characterization of a fourth histamine receptor (H(4)) expressed in bone marrow. Mol Pharmacol. 2001 Mar;59(3):420-6.
• [3] Human kidney diamine oxidase: heterologous expression, purification, and characterization. J Biol Inorg Chem. 2002 Jun;7(6):565-79.
• [4] 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.
• [5] The histamine H4 receptor: from orphan to the clinic. Front Pharmacol. 2015; 6: 65.
• [6] Azines as histamine H4 receptor antagonists. Front Biosci (Schol Ed). 2012 Jan 1;4:967-87.
• [7] Role of histamine in short- and long-term effects of methamphetamine on the developing mouse brain. J Neurochem. 2008 Nov;107(4):976-86.
• [8] 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.
• [9] 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.
• [10] 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.
• [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] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [14] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [15] Acute wake-promoting actions of JNJ-5207852, a novel, diamine-based H3 antagonist. Br J Pharmacol. 2004 Nov;143(5):649-61.
• [16] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [17] 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.
• [18] SAR110894, a potent histamine H receptor antagonist, displays procognitive effects in rodents. Pharmacol Biochem Behav. 2012 Aug;102(2):203-14.
• [19] 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.
• [20] A randomized study of H3 antagonist ABT-288 in mild-to-moderate Alzheimer's dementia.J Alzheimers Dis.2014;42(3):959-71.
• [21] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800032225)
• [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] Diamine oxidase is the amiloride-binding protein and is inhibited by amiloride analogues. J Biol Chem. 1994 Apr 1;269(13):9921-5.
• [25] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [26] Comparative Analysis of Transcriptomic Changes including mRNA and microRNA Expression Induced by the Xenoestrogens Zearalenone and Bisphenol A in Human Ovarian Cells. Toxins (Basel). 2023 Feb 9;15(2):140. doi: 10.3390/toxins15020140.
• [27] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.
• [28] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [29] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.