Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTJSZTB)

• DTT Name: Nicotinic acetylcholine receptor (nAChR)
• Synonyms: nAChR; Nicotinergic acetylcholine receptor
• Gene Name: nAChR
• DTT Type: Successful target; [1]
• BioChemical Class: Ion transport
• UniProt ID: NOUNIPROTAC
• TTD ID: T78111
• Function: After binding acetylcholine, the AChRresponds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.
• KEGG Pathway: Neuroactive ligand-receptor interaction (hsa04080)
• Reactome Pathway:
  Highly calcium permeable postsynaptic nicotinic acetylcholine receptors (R-HSA-629594)
  Highly sodium permeable acetylcholine nicotinic receptors (R-HSA-629587)

Molecular Interaction Atlas (MIA) of This DTT

5 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Atracurium	DM42HXN	Anaesthesia	9A78.6	Approved	[2]
Cotinine	DMCEZ1B	Insecticide	N.A.	Approved	[3]
Mecamylamine	DMGQFYB	Essential hypertension	BA00	Approved	[1]
Nicotine	DMWX5CO	Lung cancer	2C25.0	Approved	[4]
Pancuronium	DMB0VY8	Anaesthesia	9A78.6	Approved	[2]

12 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CYTISINE	DMUF0BJ	Tobacco dependence	6C4A.2	Phase 3	[5]
A-85380	DMHOLB7	N. A.	N. A.	Phase 2	[6]
ASM-024	DM35S2I	Asthma	CA23	Phase 2	[7]
BMS-954561	DM7XV4R	Diabetic neuropathy	8C0Z	Phase 2	[8]
Dexefaroxan	DMTY4KN	Parkinson disease	8A00.0	Phase 2	[9]
NIC-002	DMKLJMI	Nicotine dependence	6C4A.2	Phase 2	[10]
TRIDMAC	DMWU41P	Mood disorder	6A60-6E23	Phase 2	[11]
ATG002	DMB5X7Z	Diabetic foot ulcer	BD54	Phase 1/2	[12]
GANTACURIUM CHLORIDE	DMN7QBE	Anaesthesia	9A78.6	Phase 1/2	[13]
ND-0801	DMCDQX0	Attention deficit hyperactivity disorder	6A05.Z	Phase 1/2	[14]
RPI-78M	DMXKFOQ	Multiple sclerosis	8A40	Phase 1	[15]
RPI-MN	DM5OXPZ	Amyotrophic lateral sclerosis	8B60.0	Phase 1	[16]

12 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Inaperisone	DM05MCO	Pollakiuria	MF50.1	Discontinued in Preregistration	[17]
ABT-418	DMNP72I	Alzheimer disease	8A20	Discontinued in Phase 2	[18]
ABT-594	DMGMBCW	N. A.	N. A.	Discontinued in Phase 2	[19]
ORG-9273	DMW1FT0	Paralysis	8B60	Discontinued in Phase 2	[20]
RJR-2403	DMOZEN6	Cognitive impairment	6D71	Discontinued in Phase 2	[6]
SIB-1553A	DM7XC0U	Alzheimer disease	8A20	Discontinued in Phase 2	[21]
ABT-202	DMG9Y80	Pain	MG30-MG3Z	Discontinued in Phase 1	[22]
ANQ-9040	DMRQFIE	Paralysis	8B60	Discontinued in Phase 1	[23]
DBO-83	DM0JDCS	N. A.	N. A.	Terminated	[6]
NNC-90-0270	DM1SXG9	Alzheimer disease	8A20	Terminated	[24]
SIB-1663	DMO4WB8	N. A.	N. A.	Terminated	[6]
SIB-1765F	DM6MSKT	N. A.	N. A.	Terminated	[25]

3 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
8-aminoquinolines	DMN8QAF	Discovery agent	N.A.	Investigative	[26]
Epibatidine	DMAGZD8	Discovery agent	N.A.	Investigative	[21]
PROTOSTEMODIOL	DMI6TKU	Discovery agent	N.A.	Investigative	[27]

References

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• [2] Pharmacological characteristics of the inhibition of nondepolarizing neuromuscular blocking agents at human adult muscle nicotinic acetylcholine receptor. Anesthesiology. 2009 Jun;110(6):1244-52.
• [3] Functional versus chemical diversity: is biodiversity important for drug discovery. Trends Pharmacol Sci. 2002 May;23(5):225-31.
• [4] Atypical antipsychotics as noncompetitive inhibitors of alpha4beta2 and alpha7 neuronal nicotinic receptors. Neuropharmacology. 2009 Aug;57(2):183-91.
• [5] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [6] The therapeutic potential of nicotinic acetylcholine receptor agonists for pain control. Expert Opin Investig Drugs. 2001 Oct;10(10):1819-30.
• [7] Effects of ASM-024, a modulator of acetylcholine receptor function, on airway responsiveness and allergen-induced responses in patients with mild asthma. Can Respir J. 2015 Jul-Aug;22(4):230-4.
• [8] EP patent application no. 2774991, Drug delivery system for use in the treatment or diagnosis of neurological disorders.
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• [10] Therapeutic advances in the treatment of nicotine addiction: present and future. Ther Adv Chronic Dis. 2010 May; 1(3): 95-106.
• [11] Novel drugs and therapeutic targets for severe mood disorders. Neuropsychopharmacology. 2008 Aug;33(9):2080-92.
• [12] Athenagen Advances Angiogenesis Drug to Clinical Testing. Athenagen. JUNE 21, 2006.
• [13] Gantacurium and CW002 do not potentiate muscarinic receptor-mediated airway smooth muscle constriction in guinea pigs. Anesthesiology. 2010 April; 112(4): 892-899.
• [14] Drugs in Clinical Development for Attention-Deficit/Hyperactivity Disorder: Summary and Table, 2013, Volume 27, Issue 4, 245-248.
• [15] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [16] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [17] Inhibitory effect of inaperisone hydrochloride (inaperisone), a new centrally acting muscle relaxant, on the micturition reflex. Eur J Pharmacol. 1992 Mar 31;213(3):409-15.
• [18] Enhancement of sustained attention performance by the nicotinic acetylcholine receptor agonist ABT-418 in intact but not basal forebrain-lesioned rats. Psychopharmacology (Berl). 1999 May;144(2):175-82.
• [19] ABT-594 [(R)-5-(2-azetidinylmethoxy)-2-chloropyridine]: a novel, orally effective antinociceptive agent acting via neuronal nicotinic acetylcholine receptors: II. In vivo characterization. J Pharmacol Exp Ther. 1998 May;285(2):787-94.
• [20] Dose-response relation, neuromuscular blocking action, intubation conditions, and cardiovascular effects of Org 9273, a new neuromuscular blocking agent. Anesth Analg. 1991 Jun;72(6):811-6.
• [21] The potential of subtype-selective neuronal nicotinic acetylcholine receptor agonists as therapeutic agents. Life Sci. 1998;62(17-18):1601-6.
• [22] Modulators of nicotinic acetylcholine receptors as analgesics. Curr Opin Investig Drugs. 2004 Jan;5(1):76-81.
• [23] Patent US20030087306 A1.
• [24] Nicotinic agonists, antagonists, and modulators from natural sources. Cell Mol Neurobiol. 2005 Jun;25(3-4):513-52.
• [25] Interactions between a novel cholinergic ion channel agonist, SIB-1765F and L-DOPA in the reserpine model of Parkinson's disease in rats. J Pharmacol Exp Ther. 1997 Jan;280(1):393-401.
• [26] Opioids induce while nicotine suppresses apoptosis in human lung cancer cells. Cell Growth Differ. 1994 Oct;5(10):1033-40.
• [27] Alkaloids from stems and leaves of Stemona japonica and their insecticidal activities. J Nat Prod. 2008 Jan;71(1):112-6.