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

General Information of Drug (ID: DM2S5ZF)

• Drug Name: NS1738 Drug Info
• Synonyms: NS-1738

Indication

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

• Cross-matching ID:
  PubChem CID: 310378
  CAS Number: CAS 501684-93-1
  TTD Drug ID: DM2S5ZF

Molecule-Related Drug Atlas

Drug(s) Targeting Neuronal acetylcholine receptor alpha-7 (CHRNA7)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ziprasidone	DMM58JY	Bipolar disorder	6A60	Approved	[3]
ALCURONIUM	DM2U4XQ	Anaesthesia	9A78.6	Approved	[4]
AMG 386	DMQJXL4	Breast cancer	2C60-2C65	Phase 3	[5]
CYTISINE	DMUF0BJ	Tobacco dependence	6C4A.2	Phase 3	[6]
EVP-6124	DMLQO7F	Alzheimer disease	8A20	Phase 3	[7]
GTS-21	DMEN5KA	Parkinson disease	8A00.0	Phase 2	[8]
JNJ-39393406	DMUOEKM	Depression	6A70-6A7Z	Phase 2	[9]
ABT-126	DM2OS51	Alzheimer disease	8A20	Phase 2	[10]
TC-6987	DMNFP21	Asthma	CA23	Phase 2	[11]
AQW-051	DMD2RFO	Alzheimer disease	8A20	Phase 2	[12]

Drug(s) Targeting Muscarinic acetylcholine receptor M5 (CHRM5)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Promazine	DMZAL7W	Acute intermittent hepatic porphyria	5C58.11	Approved	[13]
ACECLIDINE	DMOLNCZ	Glaucoma/ocular hypertension	9C61	Approved	[14]
Pilocarpine	DMV9ADG	Glaucoma/ocular hypertension	9C61	Approved	[15]
Anisodine	DMNOSWU	Central and peripheral nervous disease	8A04-8E7Z	Approved	[16]
Atropine	DMEN6X7	Organophosphate poisoning	NE6Z	Approved	[17]
Propiverine	DMUWBIJ	Urinary incontinence	MF50.2	Approved	[18]
Umeclidinium	DM4E8O9	Chronic obstructive pulmonary disease	CA22	Approved	[19]
Cimetropium bromide	DMZHPNE	Gastric motility disorder	DA21	Approved	[20]
Butylscopolamine	DMZKXB7	Dysmenorrhea	GA34.3	Approved	[21]
Trospium	DMX6RTG	Overactive bladder	GC50.0	Approved	[22]

Drug(s) Targeting Neuronal acetylcholine receptor beta-2 (CHRNB2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CYTISINE	DMUF0BJ	Tobacco dependence	6C4A.2	Phase 3	[23]
TC-5214	DM8AM60	Palmar hyperhidrosis	EE00.00	Phase 2	[24]
SUVN-911	DMLPBVF	Major depressive disorder	6A70.3	Phase 1	[25]
AZD-9684	DMHA5ME	Thrombosis	DB61-GB90	Discontinued in Phase 2	[26]
ABT-594	DMGMBCW	N. A.	N. A.	Discontinued in Phase 2	[27]
ABT-418	DMNP72I	Alzheimer disease	8A20	Discontinued in Phase 2	[28]
HOMOEPIBATIDINE	DMHP9WV	N. A.	N. A.	Terminated	[23]
4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one	DMM9X0G	Discovery agent	N.A.	Investigative	[29]
(2S,3S)-2-Phenyl-3,5,5-trimethylmorpholin-2-ol	DMDUGZS	Discovery agent	N.A.	Investigative	[30]
(2S,3S)-2-(m-Tolyl)-3,5,5-trimethylmorpholin-2-ol	DMDUI8R	Discovery agent	N.A.	Investigative	[30]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Muscarinic acetylcholine receptor M5 (CHRM5)	TTH18TF	ACM5_HUMAN	Blocker (channel blocker)	[2]
Neuronal acetylcholine receptor alpha-7 (CHRNA7)	TTLA931	ACHA7_HUMAN	Modulator (allosteric modulator)	[2]
Neuronal acetylcholine receptor beta-2 (CHRNB2)	TT5KPZR	ACHB2_HUMAN	Blocker (channel blocker)	[2]

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: 4000).
• [2] An allosteric modulator of the alpha7 nicotinic acetylcholine receptor possessing cognition-enhancing properties in vivo. J Pharmacol Exp Ther. 2007 Oct;323(1):294-307.
• [3] The pipeline and future of drug development in schizophrenia. Mol Psychiatry. 2007 Oct;12(10):904-22.
• [4] Pharmacological characteristics and binding modes of caracurine V analogues and related compounds at the neuronal alpha7 nicotinic acetylcholine re... J Med Chem. 2007 Sep 20;50(19):4616-29.
• [5] Clinical pipeline report, company report or official report of Roche (2009).
• [6] 3,5-Bicyclic aryl piperidines: a novel class of alpha4beta2 neuronal nicotinic receptor partial agonists for smoking cessation. Bioorg Med Chem Lett. 2005 Nov 15;15(22):4889-97.
• [7] Normalizing effects of EVP-6124, an alpha-7 nicotinic partial agonist, on event-related potentials and cognition: a proof of concept, randomized trial in patients with schizophrenia. J Psychiatr Pract. 2014 Jan;20(1):12-24.
• [8] The brain alpha7 nicotinic receptor may be an important therapeutic target for the treatment of Alzheimer's disease: studies with DMXBA (GTS-21). Behav Brain Res. 2000 Aug;113(1-2):169-81.
• [9] Allosteric alpha-7 nicotinic receptor modulation and P50 sensory gating in schizophrenia: a proof-of-mechanism study. Neuropharmacology. 2013 Jan;64:197-204.
• [10] A phase 2 randomized, controlled trial of the alpha7 agonist ABT-126 in mild-to-moderate Alzheimer's dementia. Alzheimer's & Dementia: Translational Research & Clinical Interventions Volume 1, Issue 1, June 2015, Pages 81-90.
• [11] ClinicalTrials.gov (NCT01293669) Glycemic Control, Safety and Tolerability of TC-6987 Monotherapy in Type 2 Diabetes Mellitus. U.S. National Institutes of Health.
• [12] AQW051, a novel and selective nicotinic acetylcholine receptor alpha7 partial agonist, reduces l-Dopa-induced dyskinesias and extends the duration of l-Dopa effects in parkinsonian monkeys. Parkinsonism Relat Disord. 2014 Nov;20(11):1119-23.
• [13] Muscarinic cholinergic and histamine H1 receptor binding of phenothiazine drug metabolites. Life Sci. 1988;43(5):405-12.
• [14] Design, synthesis, and neurochemical evaluation of 5-(3-alkyl-1,2,4- oxadiazol-5-yl)-1,4,5,6-tetrahydropyrimidines as M1 muscarinic receptor agonists. J Med Chem. 1993 Apr 2;36(7):842-7.
• [15] Retinoic acid prevents virus-induced airway hyperreactivity and M2 receptor dysfunction via anti-inflammatory and antiviral effects. Am J Physiol Lung Cell Mol Physiol. 2009 Aug;297(2):L340-6.
• [16] Medicinal plants in therapy. Bull World Health Organ. 1985;63(6):965-81.
• [17] Additive protective effects of donepezil and nicotine against salsolinol-induced cytotoxicity in SH-SY5Y cells. Neurotox Res. 2009 Oct;16(3):194-204.
• [18] Affinity profiles of various muscarinic antagonists for cloned human muscarinic acetylcholine receptor (mAChR) subtypes and mAChRs in rat heart and submandibular gland. Life Sci. 1999;64(25):2351-8.
• [19] 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: 7354).
• [20] Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
• [21] Comparison of pharmacological effects of L- and DL-n-butyl-scopolamine in rat uterus. Yao Xue Xue Bao. 1994;29(1):24-7.
• [22] Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34.
• [23] Epibatidine isomers and analogues: structure-activity relationships. Bioorg Med Chem Lett. 2006 Nov 1;16(21):5493-7.
• [24] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [25] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [26] Blockade and activation of the human neuronal nicotinic acetylcholine receptors by atracurium and laudanosine. Anesthesiology. 2001 Apr;94(4):643-51.
• [27] The nicotinic acetylcholine receptor agonist ABT-594 increases FGF-2 expression in various rat brain regions. Neuroreport. 1999 Dec 16;10(18):3909-13.
• [28] Nicotine, brain nicotinic receptors, and neuropsychiatric disorders. Arch Med Res. 2000 Mar-Apr;31(2):131-44.
• [29] Discovery of N-{1-[3-(3-oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4-yl}-2-phenylacetamide (Lu AE51090): an allosteric muscarinic M1 rec... J Med Chem. 2010 Sep 9;53(17):6386-97.
• [30] Synthesis and characterization of in vitro and in vivo profiles of hydroxybupropion analogues: aids to smoking cessation. J Med Chem. 2010 Jun 24;53(12):4731-48.