Target Information

Target General Information

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Target ID

T78111 (Former ID: TTDS00303)

Target Name

Nicotinic acetylcholine receptor (nAChR)

Synonyms

nAChR; Nicotinergic acetylcholine receptor

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Gene Name

NO-GeName

Target Type

Successful target

[1]

Disease

[+] 4 Target-related Diseases

Corneal disease [ICD-11: 9A76-9A78]

Essential hypertension [ICD-11: BA00]

Insecticide [ICD-11: N.A.]

Nicotine use disorder [ICD-11: 6C4A]

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.

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BioChemical Class

Ion transport

UniProt ID

NOUNIPROTAC

Drugs and Modes of Action

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Approved Drug(s)

[+] 4 Approved Drugs

Atracurium

Drug Info

Approved

Anaesthesia

[3]

Cotinine

Drug Info

Approved

Insecticide

[2]

Nicotine

Drug Info

Approved

Nicotine dependence

[4], [5]

Pancuronium

Drug Info

Approved

Anaesthesia

[6], [7]

Clinical Trial Drug(s)

[+] 9 Clinical Trial Drugs

CYTISINE

Drug Info

Phase 3

Tobacco dependence

[8]

ASM-024

Drug Info

Phase 2

Asthma

[10]

BMS-954561

Drug Info

Phase 2

Diabetic neuropathy

[11]

Dexefaroxan

Drug Info

Phase 2

Parkinson disease

[12]

NIC-002

Drug Info

Phase 2

Nicotine dependence

[13]

ATG002

Drug Info

Phase 1/2

Diabetic foot ulcer

[15]

GANTACURIUM CHLORIDE

Drug Info

Phase 1/2

Anaesthesia

[16]

RPI-78M

Drug Info

Phase 1

Multiple sclerosis

[17], [18]

RPI-MN

Drug Info

Phase 1

Amyotrophic lateral sclerosis

[18]

Discontinued Drug(s)

[+] 9 Discontinued Drugs

Inaperisone

Drug Info

Discontinued in Preregistration

Pollakiuria

[19]

ABT-418

Drug Info

Discontinued in Phase 2

Alzheimer disease

[20]

ORG-9273

Drug Info

Discontinued in Phase 2

Paralysis

[21]

RJR-2403

Drug Info

Discontinued in Phase 2

Cognitive impairment

[22], [23]

SIB-1553A

Drug Info

Discontinued in Phase 2

Alzheimer disease

[24]

ABT-202

Drug Info

Discontinued in Phase 1

Pain

[25]

ANQ-9040

Drug Info

Discontinued in Phase 1

Paralysis

[26]

Dianicline+rimonabant

Drug Info

Terminated

Tobacco dependence

[27]

NNC-90-0270

Drug Info

Terminated

Alzheimer disease

[28]

Mode of Action

[+] 4 Modes of Action

Antagonist

[+] 6 Antagonist drugs

Atracurium

Drug Info

[7], [29], [30]

Nicotine

Drug Info

[32], [33]

Pancuronium

Drug Info

[7]

CYTISINE

Drug Info

[8]

RPI-78M

Drug Info

[17], [18]

RPI-MN

Drug Info

[18]

Modulator

[+] 7 Modulator drugs

Cotinine

Drug Info

[31]

BMS-954561

Drug Info

[35]

GANTACURIUM CHLORIDE

Drug Info

[39]

Inaperisone

Drug Info

[40]

ORG-9273

Drug Info

[21], [2]

ABT-202

Drug Info

[46]

ANQ-9040

Drug Info

[47], [2]

Agonist

[+] 13 Agonist drugs

ASM-024

Drug Info

[34]

Dexefaroxan

Drug Info

[36]

ATG002

Drug Info

[38]

ABT-418

Drug Info

[41]

ABT-594

Drug Info

[42], [43]

RJR-2403

Drug Info

[44]

SIB-1553A

Drug Info

[45]

DBO-83

Drug Info

[44]

Dianicline+rimonabant

Drug Info

[48]

NNC-90-0270

Drug Info

[28]

SIB-1663

Drug Info

[44]

SIB-1765F

Drug Info

[49]

Epibatidine

Drug Info

[45]

Inhibitor

[+] 1 Inhibitor drugs

PROTOSTEMODIOL

Drug Info

[50]

Drug Property Profile of Target

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(1) Molecular Weight (mw) based Drug Clustering

(2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering

(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering

(4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering

(5) Rotatable Bond Count (rotbonds) based Drug Clustering

(6) Topological Polar Surface Area (polararea) based Drug Clustering

"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five

Co-Targets

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Co-Targets

Co-Targets Info

Target Affiliated Biological Pathways

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KEGG Pathway

[+] 1 KEGG Pathways

Neuroactive ligand-receptor interaction

Reactome

[+] 2 Reactome Pathways

Highly sodium permeable acetylcholine nicotinic receptors

Highly calcium permeable postsynaptic nicotinic acetylcholine receptors

WikiPathways

[+] 1 WikiPathways

Neurotransmitter Receptor Binding And Downstream Transmission In The Postsynaptic Cell

Target-Related Models and Studies

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Target Validation

Target Validation Info

Target QSAR Model

References

Top

REF 1

Mecamylamine (Inversine): an old antihypertensive with new research directions. J Hum Hypertens. 2002 Jul;16(7):453-7.

REF 2

Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015

REF 3

A preliminary assessment of atracurium, a new competitive neuromuscular blocking agent. Acta Anaesthesiol Scand. 1981 Feb;25(1):67-9.

REF 4

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: 2585).

REF 5

FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 074611.

REF 6

REF 7

Pharmacological characteristics of the inhibition of nondepolarizing neuromuscular blocking agents at human adult muscle nicotinic acetylcholine receptor. Anesthesiology. 2009 Jun;110(6):1244-52.

REF 8

Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)

REF 9

Novel drugs and therapeutic targets for severe mood disorders. Neuropsychopharmacology. 2008 Aug;33(9):2080-92.

REF 10

ClinicalTrials.gov (NCT01190826) Safety, Tolerability and Clinical Activity of ASM-024 in Stable Moderate Asthma. U.S. National Institutes of Health.

REF 11

ClinicalTrials.gov (NCT01314222) Diabetic Peripheral Neuropathic Pain (DPNP). U.S. National Institutes of Health.

REF 12

Effects of the alpha 2-adrenoreceptor antagonist dexefaroxan on neurogenesis in the olfactory bulb of the adult rat in vivo: selective protection against neuronal death. Neuroscience. 2003;117(2):281-91.

REF 13

ClinicalTrials.gov (NCT00369616) Efficacy and Safety of Nicotine-Qbeta Vaccine in Smokers. U.S. National Institutes of Health.

REF 14

ClinicalTrials.gov (NCT01174355) A Study of ND0801 in Attention Deficit/Hyperactivity Disorder (ADHD). U.S. National Institutes of Health.

REF 15

ClinicalTrials.gov (NCT00316537) Safety and Preliminary Efficacy Study of Nicotine Gel to Treat Diabetic Foot Ulcers. U.S. National Institutes of Health.

REF 16

ClinicalTrials.gov (NCT00235976) The Efficacy and Safety of Gantacurium Chloride for Injection in Tracheal Intubation in Healthy Adult Patients Undergoing Surgery Under General Anesthesia. U.S. National Institutes of Health.

REF 17

Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)

REF 18

Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)

REF 19

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003120)

REF 20

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004036)

REF 21

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.

REF 22

REF 23

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007149)

REF 24

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800009631)

REF 25

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800015975)

REF 26

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003547)

REF 27

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800027143)

REF 28

Nicotinic agonists, antagonists, and modulators from natural sources. Cell Mol Neurobiol. 2005 Jun;25(3-4):513-52.

REF 29

Neuromuscular block. Br J Pharmacol. 2006 Jan;147 Suppl 1:S277-86.

REF 30

Blockade and activation of the human neuronal nicotinic acetylcholine receptors by atracurium and laudanosine. Anesthesiology. 2001 Apr;94(4):643-51.

REF 31

Functional versus chemical diversity: is biodiversity important for drug discovery. Trends Pharmacol Sci. 2002 May;23(5):225-31.

REF 32

Atypical antipsychotics as noncompetitive inhibitors of alpha4beta2 and alpha7 neuronal nicotinic receptors. Neuropharmacology. 2009 Aug;57(2):183-91.

REF 33

Development and optimization of a high-throughput electrophysiology assay for neuronal alpha4beta2 nicotinic receptors. J Neurosci Methods. 2009 Aug 30;182(1):17-24.

REF 34

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.

REF 35

EP patent application no. 2774991, Drug delivery system for use in the treatment or diagnosis of neurological disorders.

REF 36

The pipeline and future of drug development in schizophrenia. Mol Psychiatry. 2007 Oct;12(10):904-22.

REF 37

Therapeutic advances in the treatment of nicotine addiction: present and future. Ther Adv Chronic Dis. 2010 May; 1(3): 95-106.

REF 38

Athenagen Advances Angiogenesis Drug to Clinical Testing. Athenagen. JUNE 21, 2006.

REF 39

Gantacurium and CW002 do not potentiate muscarinic receptor-mediated airway smooth muscle constriction in guinea pigs. Anesthesiology. 2010 April; 112(4): 892-899.

REF 40

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.

REF 41

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.

REF 42

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.

REF 43

The nicotinic acetylcholine receptor agonist ABT-594 increases FGF-2 expression in various rat brain regions. Neuroreport. 1999 Dec 16;10(18):3909-13.

REF 44

The therapeutic potential of nicotinic acetylcholine receptor agonists for pain control. Expert Opin Investig Drugs. 2001 Oct;10(10):1819-30.

REF 45

The potential of subtype-selective neuronal nicotinic acetylcholine receptor agonists as therapeutic agents. Life Sci. 1998;62(17-18):1601-6.

REF 46

Modulators of nicotinic acetylcholine receptors as analgesics. Curr Opin Investig Drugs. 2004 Jan;5(1):76-81.

REF 47

Patent US20030087306 A1.

REF 48

Emerging drugs for the treatment of tobacco dependence. Expert Opin Emerg Drugs. 2009 Mar;14(1):23-32.

REF 49

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.

REF 50

Alkaloids from stems and leaves of Stemona japonica and their insecticidal activities. J Nat Prod. 2008 Jan;71(1):112-6.

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