Target Information
| Target General Information | Top | |||||
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| Target ID |
T63967
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| Target Name |
Neuronal acetylcholine receptor alpha-4/beta-2 (CHRNA4/B2)
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| Synonyms |
CHRN; nAChR
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| Gene Name |
CHRNA4-CHRNB2
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Corneal disease [ICD-11: 9A76-9A78] | |||||
| 2 | Nicotine use disorder [ICD-11: 6C4A] | |||||
| Function |
After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane permeable to sodiun ions.
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| BioChemical Class |
Neurotransmitter receptor
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| UniProt ID | ||||||
| Sequence |
MELGGPGAPRLLPPLLLLLGTGLLRASSHVETRAHAEERLLKKLFSGYNKWSRPVANISD
VVLVRFGLSIAQLIDVDEKNQMMTTNVWVKQEWHDYKLRWDPADYENVTSIRIPSELIWR PDIVLYNNADGDFAVTHLTKAHLFHDGRVQWTPPAIYKSSCSIDVTFFPFDQQNCTMKFG SWTYDKAKIDLVNMHSRVDQLDFWESGEWVIVDAVGTYNTRKYECCAEIYPDITYAFVIR RLPLFYTINLIIPCLLISCLTVLVFYLPSECGEKITLCISVLLSLTVFLLLITEIIPSTS LVIPLIGEYLLFTMIFVTLSIVITVFVLNVHHRSPRTHTMPTWVRRVFLDIVPRLLLMKR PSVVKDNCRRLIESMHKMASAPRFWPEPEGEPPATSGTQSLHPPSPSFCVPLDVPAEPGP SCKSPSDQLPPQQPLEAEKASPHPSPGPCRPPHGTQAPGLAKARSLSVQHMSSPGEAVEG GVRCRSRSIQYCVPRDDAAPEADGQAAGALASRNTHSAELPPPDQPSPCKCTCKKEPSSV SPSATVKTRSTKAPPPHLPLSPALTRAVEGVQYIADHLKAEDTDFSVKEDWKYVAMVIDR IFLWMFIIVCLLGTVGLFLPPWLAGMI Click to Show/Hide
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| Drugs and Modes of Action | Top | |||||
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| Approved Drug(s) | [+] 2 Approved Drugs | + | ||||
| 1 | Metocurine Iodide | Drug Info | Approved | Anaesthesia | [2] | |
| 2 | Varenicline | Drug Info | Approved | Smoking dependence | [1], [3] | |
| Clinical Trial Drug(s) | [+] 6 Clinical Trial Drugs | + | ||||
| 1 | AZD-1446 | Drug Info | Phase 2 | Alzheimer disease | [4] | |
| 2 | CP-601927 | Drug Info | Phase 2 | Gastrointestinal disease | [5] | |
| 3 | Sofinicline | Drug Info | Phase 2 | Attention deficit hyperactivity disorder | [6] | |
| 4 | TC-6499-12 | Drug Info | Phase 2 | Irritable bowel syndrome | [7] | |
| 5 | SUVN 911 | Drug Info | Phase 1 | Major depressive disorder | [8] | |
| 6 | TC-2216 | Drug Info | Phase 1 | Mood disorder | [9] | |
| Discontinued Drug(s) | [+] 5 Discontinued Drugs | + | ||||
| 1 | Dianicline | Drug Info | Discontinued in Phase 3 | Tobacco dependence | [10] | |
| 2 | ABT-089 | Drug Info | Discontinued in Phase 2 | Dementia | [11] | |
| 3 | Ispronicline | Drug Info | Discontinued in Phase 2 | Alzheimer disease | [12] | |
| 4 | TC-2696 | Drug Info | Discontinued in Phase 2 | Pain | [13] | |
| 5 | SIB-1508Y | Drug Info | Terminated | Parkinson disease | [15], [16] | |
| Preclinical Drug(s) | [+] 1 Preclinical Drugs | + | ||||
| 1 | A-366833 | Drug Info | Preclinical | Pain | [14] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Modulator | [+] 13 Modulator drugs | + | ||||
| 1 | Metocurine Iodide | Drug Info | [17] | |||
| 2 | Varenicline | Drug Info | [1] | |||
| 3 | AZD-1446 | Drug Info | [18] | |||
| 4 | CP-601927 | Drug Info | [19] | |||
| 5 | Sofinicline | Drug Info | [6] | |||
| 6 | TC-6499-12 | Drug Info | [20] | |||
| 7 | TC-2216 | Drug Info | [22] | |||
| 8 | Dianicline | Drug Info | [23] | |||
| 9 | ABT-089 | Drug Info | [24] | |||
| 10 | Ispronicline | Drug Info | [25] | |||
| 11 | TC-2696 | Drug Info | [26] | |||
| 12 | A-366833 | Drug Info | [27] | |||
| 13 | SIB-1508Y | Drug Info | [28] | |||
| Antagonist | [+] 1 Antagonist drugs | + | ||||
| 1 | SUVN 911 | Drug Info | [21] | |||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "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 | Top | |||||
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| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| References | Top | |||||
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| REF 1 | 2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101. | |||||
| REF 2 | Drug information of Metocurine Iodide, 2008. eduDrugs. | |||||
| REF 3 | 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: 5459). | |||||
| REF 4 | ClinicalTrials.gov (NCT01012375) Study to Investigate the Efficacy and Tolerability of AZD1446 in Adult ADHD Patients.. U.S. National Institutes of Health. | |||||
| REF 5 | ClinicalTrials.gov (NCT01098240) A Study Of The Efficacy And Safety Of CP-601,927 Augmentation Of Antidepressant Therapy In Major Depression. U.S. National Institutes of Health. | |||||
| REF 6 | Sofinicline: a novel nicotinic acetylcholine receptor agonist in the treatment of attention-deficit/hyperactivity disorder. Expert Opin Investig Drugs. 2014 Aug;23(8):1157-63. | |||||
| REF 7 | ClinicalTrials.gov (NCT01149200) Proof-of-Principle Study of TC-6499 in the Treatment of Constipation Predominant Irritable Bowel Syndrome (IBS). U.S. National Institutes of Health. | |||||
| REF 8 | ClinicalTrials.gov (NCT03551288) Effect of Food, Gender, and Age on the Pharmacokinetic Profile of SUVN-911 in Healthy Subjects (SUVN-911). U.S. National Institutes of Health. | |||||
| REF 9 | ClinicalTrials.gov (NCT00583544) A Safety and Tolerability Single Ascending Dose Study in Healthy Volunteers. U.S. National Institutes of Health. | |||||
| REF 10 | Emerging drugs for the treatment of tobacco dependence. Expert Opin Emerg Drugs. 2009 Mar;14(1):23-32. | |||||
| REF 11 | Emerging drugs for attention-deficit/hyperactivity disorder. Expert Opin Emerg Drugs. 2007 Sep;12(3):423-34. | |||||
| REF 12 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800011083) | |||||
| REF 13 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800021012) | |||||
| REF 14 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800020139) | |||||
| REF 15 | Pharmacological characterization of (S)-(2)-5-ethynyl-3-(1-methyl-2-pyrrolidinyl)pyridine HCl (SIB-1508Y, Altinicline), a novel nicotinic acetylcholine receptor agonist. Brain Res. 2008 Oct 9;1234:16-24. | |||||
| REF 16 | Recombinant human receptors and functional assays in the discovery of altinicline (SIB-1508Y), a novel acetylcholine-gated ion channel (nAChR) agonist. Pharm Acta Helv. 2000 Mar;74(2-3):125-30. | |||||
| REF 17 | NMR study of general anesthetic interaction with nAChR beta2 subunit.Biophys J.2008 Mar 1;94(5):1681-8. | |||||
| REF 18 | A randomized, double-blind, placebo-controlled crossover study of 4 2* nicotinic acetylcholine receptor agonist AZD1446 (TC-6683) in adults with attention-deficit/hyperactivity disorder.Psychopharmacology (Berl). 2014 Mar;231(6):1251-65. | |||||
| REF 19 | Toxicity study in juvenile rats with the alpha4beta2 nicotinic acetylcholine receptor partial agonist CP-601,927. Birth Defects Res B Dev Reprod Toxicol. 2011 Aug;92(4):323-32. | |||||
| REF 20 | Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41. | |||||
| REF 21 | Discovery and Development of 3-(6-Chloropyridine-3-yloxymethyl)-2-azabicyclo[3.1.0]hexane Hydrochloride (SUVN-911): A Novel, Potent, Selective, and Orally Active Neuronal Nicotinic Acetylcholine alpha42 Receptor Antagonist for the Treatment of Depression. J Med Chem. 2020 Mar 26;63(6):2833-2853. | |||||
| REF 22 | TC-5214 (S-(+)-mecamylamine): a neuronal nicotinic receptor modulator with antidepressant activity.CNS Neurosci Ther.2008 Winter;14(4):266-77. | |||||
| REF 23 | Dianicline, a novel 42 nicotinic acetylcholine receptor partial agonist, for smoking cessation: a randomized placebo-controlled clinical trial.Nicotine Tob Res.2011 Jan;13(1):1-6. | |||||
| REF 24 | Selectivity of ABT-089 for alpha4beta2* and alpha6beta2* nicotinic acetylcholine receptors in brain.Biochem Pharmacol.2009 Oct 1;78(7):795-802. | |||||
| REF 25 | Ispronicline: a novel alpha4beta2 nicotinic acetylcholine receptor-selective agonist with cognition-enhancing and neuroprotective properties. J Mol Neurosci. 2006;30(1-2):19-20. | |||||
| REF 26 | alpha4beta2 Nicotinic receptors play a role in the nAChR-mediated decline in L-dopa-induced dyskinesias in parkinsonian rats. Neuropharmacology. 2013 Aug;71:191-203. | |||||
| REF 27 | Antinociceptive activity of alpha4beta2* neuronal nicotinic receptor agonist A-366833 in experimental models of neuropathic and inflammatory pain. Eur J Pharmacol. 2011 Oct 1;668(1-2):155-62. | |||||
| REF 28 | Nicotinic Receptors in Neurodegeneration | |||||
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