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

General Information of Drug (ID: DMR3E4L)

• Drug Name: Irdabisant Drug Info
• Synonyms: CEP-26401

Indication

Disease Entry	ICD 11	Status	REF
Cognitive impairment	6D71	Phase 1	[1]

• Cross-matching ID:
  PubChem CID: 25070031
  CAS Number: CAS 1005402-19-6
  TTD Drug ID: DMR3E4L

Molecule-Related Drug Atlas

Drug(s) Targeting Histamine H3 receptor (H3R)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Pitolisant	DM8RFNJ	Excessive daytime sleepiness	MG42	Approved	[4]
SUVN-G3031	DM3BO8G	Cognitive impairment	6D71	Phase 3	[5]
JNJ-17216498	DM1GRCU	Narcolepsy	7A20	Phase 2	[6]
GSK239512	DMBJMZC	Alzheimer disease	8A20	Phase 2	[7]
JNJ-39220675	DM0WY3H	Alcohol dependence	6C40.2	Phase 2	[8]
AZD-5213	DMOZ04X	Alzheimer disease	8A20	Phase 2	[9]
Bavisant	DM6CVZ5	Attention deficit hyperactivity disorder	6A05.Z	Phase 2	[10]
ABT-288	DM7X54F	Alzheimer disease	8A20	Phase 2	[11]
SAR-110894	DMCLEXM	Alzheimer disease	8A20	Phase 2	[9]
ABT-652	DMLEO2Z	Diabetic neuropathy	8C0Z	Phase 2	[12]

Drug(s) Affected By Histamine H3 receptor (HRH3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[13]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[14]
Benzo(a)pyrene	DMN7J43	N. A.	N. A.	Phase 1	[15]
Clobenpropit	DM537OH	Discovery agent	N.A.	Investigative	[16]
N-[3H]alpha-methylhistamine	DMWDCV1	Discovery agent	N.A.	Investigative	[17]
Trichostatin A	DM9C8NX	Solid tumour/cancer	2A00-2F9Z	Investigative	[18]
Guanosine-5'-Triphosphate	DMV2OJX	Discovery agent	N.A.	Investigative	[3]

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	Antagonist	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Histamine H3 receptor (HRH3)	OT7GF3AI	HRH3_HUMAN	Protein Interaction/Cellular Processes	[3]

References

• [1] ClinicalTrials.gov (NCT01903824) Pharmacokinetics and Pharmacodynamics (PK/PD) of CEP-26401 in Healthy Subjects. U.S. National Institutes of Health.
• [2] CEP-26401 (irdabisant), a potent and selective histamine H receptor antagonist/inverse agonist with cognition-enhancing and wake-promoting activities. J Pharmacol Exp Ther. 2012 Jan;340(1):124-33.
• [3] Discovery and characterization of 6-{4-[3-(R)-2-methylpyrrolidin-1-yl)propoxy]phenyl}-2H-pyridazin-3-one (CEP-26401, irdabisant): a potent, selective histamine H3 receptor inverse agonist. J Med Chem. 2011 Jul 14;54(13):4781-92. doi: 10.1021/jm200401v. Epub 2011 Jun 2.
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [5] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [6] Acute wake-promoting actions of JNJ-5207852, a novel, diamine-based H3 antagonist. Br J Pharmacol. 2004 Nov;143(5):649-61.
• [7] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [8] 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.
• [9] SAR110894, a potent histamine H receptor antagonist, displays procognitive effects in rodents. Pharmacol Biochem Behav. 2012 Aug;102(2):203-14.
• [10] 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.
• [11] A randomized study of H3 antagonist ABT-288 in mild-to-moderate Alzheimer's dementia.J Alzheimers Dis.2014;42(3):959-71.
• [12] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800032225)
• [13] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [14] 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.
• [15] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [16] Molecular determinants of ligand binding modes in the histamine H(4) receptor: linking ligand-based three-dimensional quantitative structure-activity relationship (3D-QSAR) models to in silico guided receptor mutagenesis studies. J Med Chem. 2011 Dec 8;54(23):8136-47. doi: 10.1021/jm201042n. Epub 2011 Nov 7.
• [17] Discovery of two clinical histamine H(3) receptor antagonists: trans-N-ethyl-3-fluoro-3-[3-fluoro-4-(pyrrolidinylmethyl)phenyl]cyclobutanecarboxamide (PF-03654746) and trans-3-fluoro-3-[3-fluoro-4-(pyrrolidin-1-ylmethyl)phenyl]-N-(2-methylpropyl)cyclobutanecarboxamide (PF-03654764). J Med Chem. 2011 Nov 10;54(21):7602-20. doi: 10.1021/jm200939b. Epub 2011 Oct 7.
• [18] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.