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

General Information of Drug (ID: DM4VYP0)

• Drug Name: CONESSINE Drug Info
• Synonyms: conessine; Roquessine; Neriine; 546-06-5; Conessinum; Wrightine; Conessin; UNII-EZ38J9BBDF; NSC 119994; EZ38J9BBDF; Konessin; CHEBI:27965; GPLGAQQQNWMVMM-MYAJQUOBSA-N; Conessine [INN]; N,N-dimethylcon-5-enin-3beta-amine; ST066907; Conesina [INN-Spanish]; Conessinum [INN-Latin]; DSSTox_CID_26000; DSSTox_RID_81281; DSSTox_GSID_46000; 3beta-(Dimethylamino)con-5-ene; Conesina; EINECS 208-897-2; BRN 4702160; Con-5-enine, 3.beta.-(dimethylamino)-; ((2S,5S,12S,16S,1R,9R,13R)-6,7,13-trimethyl-7-azapentacyclo[10.8.0.0< 2,9> 5, 9&gt

Indication

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

• Cross-matching ID:
  PubChem CID: 441082
  ChEBI ID: CHEBI:27965
  CAS Number: CAS 546-06-5
  TTD Drug ID: DM4VYP0

Molecule-Related Drug Atlas

Drug(s) Targeting Adrenergic receptor alpha-2C (ADRA2C)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
MOXONIDINE	DMGFB0E	Alcohol dependence	6C40.2	Approved	[4]
Dihydroergocristine	DM5SQ1G	Alcohol dependence	6C40.2	Approved	[5]
Brimonidine	DMQLT4N	Ocular hypertension	9C61.01	Approved	[6]
Amosulalol	DML8QSZ	Hypertension	BA00-BA04	Approved	[7]
Amezinium	DM6I2WQ	Hypotension	BA20-BA21	Approved	[8]
Propylhexedrine	DMTBW2O	Obesity	5B81	Approved	[9]
Tetrahydrozoline	DMT57WC	Ocular disease	1F00.1Z	Approved	[10]
Rilmenidine	DM13PQW	Hypertension	BA00-BA04	Approved	[11]
Xylometazoline	DMKV32D	Allergic rhinitis	CA08.0	Phase 4	[12]
TNX-102	DMO1234	Fibromyalgia	MG30.01	Phase 3	[13]

Drug(s) Targeting Histamine H3 receptor (H3R)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Pitolisant	DM8RFNJ	Excessive daytime sleepiness	MG42	Approved	[14]
SUVN-G3031	DM3BO8G	Cognitive impairment	6D71	Phase 3	[15]
JNJ-17216498	DM1GRCU	Narcolepsy	7A20	Phase 2	[16]
GSK239512	DMBJMZC	Alzheimer disease	8A20	Phase 2	[17]
JNJ-39220675	DM0WY3H	Alcohol dependence	6C40.2	Phase 2	[18]
AZD-5213	DMOZ04X	Alzheimer disease	8A20	Phase 2	[19]
Bavisant	DM6CVZ5	Attention deficit hyperactivity disorder	6A05.Z	Phase 2	[20]
ABT-288	DM7X54F	Alzheimer disease	8A20	Phase 2	[21]
SAR-110894	DMCLEXM	Alzheimer disease	8A20	Phase 2	[19]
ABT-652	DMLEO2Z	Diabetic neuropathy	8C0Z	Phase 2	[22]

Drug(s) Targeting Trypanosoma Trypanothione reductase (Trypano TPR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Vitamin A	DMJ2AH4	Night blindness	9D45	Approved	[23]
Bivalirudin	DMECRX1	Thrombocytopenia	3B64	Approved	[24]
Flavin-Adenine Dinucleotide	DM5S4GK	Discovery agent	N.A.	Investigative	[25]
Maleic Acid	DM4L0R7	Discovery agent	N.A.	Investigative	[26]
1-(2'-chlorophenyl)penta-1,4-dien-3-one	DMKTZSY	Discovery agent	N.A.	Investigative	[27]
CEPHARANTINE	DMCE3NA	Discovery agent	N.A.	Investigative	[1]
Trypanothione	DMDUGQ1	Discovery agent	N.A.	Investigative	[25]
N-(5-chloro-2-(phenylthio)phenyl)butyramide	DMHZ256	Discovery agent	N.A.	Investigative	[28]
N1,N2-bis(dihydrocaffeoyl)spermine	DMSDVGQ	Discovery agent	N.A.	Investigative	[1]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Adrenergic receptor alpha-2C (ADRA2C)	TT2NUT5	ADA2C_HUMAN	Inhibitor	[2]
Histamine H3 receptor (H3R)	TT9JNIC	HRH3_HUMAN	Inhibitor	[3]
Trypanosoma Trypanothione reductase (Trypano TPR)	TTRTKPV	TYTR_TRYBB	Inhibitor	[1]

References

• [1] The use of natural product scaffolds as leads in the search for trypanothione reductase inhibitors. Bioorg Med Chem. 2008 Jul 15;16(14):6689-95.
• [2] The alkaloid conessine and analogues as potent histamine H3 receptor antagonists. J Med Chem. 2008 Sep 11;51(17):5423-30.
• [3] Design of a new histamine H3 receptor antagonist chemotype: (3aR,6aR)-5-alkyl-1-aryl-octahydropyrrolo[3,4-b]pyrroles, synthesis, and structure-acti... J Med Chem. 2009 Aug 13;52(15):4640-9.
• [4] Synthesis and pharmacologic evaluation of 2-endo-amino-3-exo-isopropylbicyclo[2.2.1]heptane: a potent imidazoline1 receptor specific agent. J Med Chem. 1996 Mar 15;39(6):1193-5.
• [5] Effect of dihydroergocristine on blood pressure and activity at peripheral alpha-adrenoceptors in pithed rats. Eur J Pharmacol. 1984 Jan 13;97(1-2):21-7.
• [6] 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: 520).
• [7] Effects of amosulalol, a combined alpha 1- and beta-adrenoceptor-blocking agent, on ischemic myocardial energy metabolism in dogs. J Pharm Sci. 1993 Mar;82(3):291-5.
• [8] Pharmacology of amezinium, a novel antihypotensive drug. III. Studies on the mechanism of action. Arzneimittelforschung. 1981;31(9a):1558-65.
• [9] Airway compromise and delayed death following attempted central vein injection of propylhexedrine. J Emerg Med. 1994 Nov-Dec;12(6):795-7.
• [10] Prolonged cardiovascular effects after unintentional ingestion of tetrahydrozoline. Clin Toxicol (Phila). 2008 Feb;46(2):171-2.
• [11] Rilmenidine-induced ocular hypotension: role of imidazoline1 and alpha 2 receptors. Curr Eye Res. 1996 Sep;15(9):943-50.
• [12] Alpha-adrenoceptor agonistic activity of oxymetazoline and xylometazoline. Fundam Clin Pharmacol. 2010 Dec;24(6):729-39.
• [13] Clinical pipeline report, company report or official report of Tonix Pharmaceuticals.
• [14] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [15] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [16] Acute wake-promoting actions of JNJ-5207852, a novel, diamine-based H3 antagonist. Br J Pharmacol. 2004 Nov;143(5):649-61.
• [17] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [18] 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.
• [19] SAR110894, a potent histamine H receptor antagonist, displays procognitive effects in rodents. Pharmacol Biochem Behav. 2012 Aug;102(2):203-14.
• [20] 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.
• [21] A randomized study of H3 antagonist ABT-288 in mild-to-moderate Alzheimer's dementia.J Alzheimers Dis.2014;42(3):959-71.
• [22] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800032225)
• [23] Opportunities and challenges in antiparasitic drug discovery. Nat Rev Drug Discov. 2005 Sep;4(9):727-40.
• [24] 8-Methoxy-naphtho[2,3-b]thiophen-4,9-quinone, a non-competitive inhibitor of trypanothione reductase. Mem Inst Oswaldo Cruz. 2003 Jun;98(4):565-8.
• [25] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [26] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [27] Irreversible inactivation of trypanothione reductase by unsaturated Mannich bases: a divinyl ketone as key intermediate. J Med Chem. 2005 Nov 17;48(23):7400-10.
• [28] Antitrypanosomal, antileishmanial, and antimalarial activities of quaternary arylalkylammonium 2-amino-4-chlorophenyl phenyl sulfides, a new class ... J Med Chem. 2005 Dec 15;48(25):8087-97.