Target Information
Target General Information | Top | |||||
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Target ID |
T34429
(Former ID: TTDS00520)
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Target Name |
Neuronal acetylcholine receptor alpha-7 (CHRNA7)
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Synonyms |
Nicotinic acetylcholine receptor subunit alpha 7; Nicotinic acetylcholine receptor alpha7; CHRNA7; Alpha7 nicotinic receptor; Alpha7 nAChR; Alpha-7 nAChR; Alpha(7) nicotinic receptor
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Gene Name |
CHRNA7
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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 | Schizophrenia [ICD-11: 6A20] | |||||
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. The channel is blocked by alpha-bungarotoxin.
Click to Show/Hide
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BioChemical Class |
Neurotransmitter receptor
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UniProt ID | ||||||
Sequence |
MRCSPGGVWLALAASLLHVSLQGEFQRKLYKELVKNYNPLERPVANDSQPLTVYFSLSLL
QIMDVDEKNQVLTTNIWLQMSWTDHYLQWNVSEYPGVKTVRFPDGQIWKPDILLYNSADE RFDATFHTNVLVNSSGHCQYLPPGIFKSSCYIDVRWFPFDVQHCKLKFGSWSYGGWSLDL QMQEADISGYIPNGEWDLVGIPGKRSERFYECCKEPYPDVTFTVTMRRRTLYYGLNLLIP CVLISALALLVFLLPADSGEKISLGITVLLSLTVFMLLVAEIMPATSDSVPLIAQYFAST MIIVGLSVVVTVIVLQYHHHDPDGGKMPKWTRVILLNWCAWFLRMKRPGEDKVRPACQHK QRRCSLASVEMSAVAPPPASNGNLLYIGFRGLDGVHCVPTPDSGVVCGRMACSPTHDEHL LHGGQPPEGDPDLAKILEEVRYIANRFRCQDESEAVCSEWKFAACVVDRLCLMAFSVFTI ICTIGILMSAPNFVEAVSKDFA Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
HIT2.0 ID | T34I45 |
Drugs and Modes of Action | Top | |||||
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Approved Drug(s) | [+] 2 Approved Drugs | + | ||||
1 | ALCURONIUM | Drug Info | Approved | Anaesthesia | [2], [3] | |
2 | Ziprasidone | Drug Info | Approved | Schizophrenia | [1], [4], [5] | |
Clinical Trial Drug(s) | [+] 13 Clinical Trial Drugs | + | ||||
1 | AMG 386 | Drug Info | Phase 3 | Neuropathic pain | [6] | |
2 | CYTISINE | Drug Info | Phase 3 | Tobacco dependence | [7] | |
3 | EVP-6124 | Drug Info | Phase 3 | Schizophrenia | [8] | |
4 | ABT-126 | Drug Info | Phase 2 | Schizophrenia | [9] | |
5 | AQW-051 | Drug Info | Phase 2 | Alzheimer disease | [10], [11] | |
6 | GTS-21 | Drug Info | Phase 2 | Parkinson disease | [12] | |
7 | JNJ-39393406 | Drug Info | Phase 2 | Depression | [7] | |
8 | MEM-3454 | Drug Info | Phase 2 | Schizophrenia | [1] | |
9 | TC-6987 | Drug Info | Phase 2 | Asthma | [13] | |
10 | AVL-3288 | Drug Info | Phase 1 | Cognitive impairment | [14] | |
11 | BMS-933043 | Drug Info | Phase 1 | Psychiatric disorder | [15] | |
12 | BNC375 | Drug Info | Phase 1 | Cognitive impairment | [16], [17] | |
13 | R4996 | Drug Info | Phase 1 | Neurological disorder | [18] | |
Discontinued Drug(s) | [+] 4 Discontinued Drugs | + | ||||
1 | AZD-9684 | Drug Info | Discontinued in Phase 2 | Thrombosis | [19] | |
2 | AZD0328 | Drug Info | Discontinued in Phase 2 | Alzheimer disease | [20], [21] | |
3 | ABT-107 | Drug Info | Discontinued in Phase 1 | Attention deficit hyperactivity disorder | [22] | |
4 | PNU-282987 | Drug Info | Terminated | Schizophrenia | [24], [1] | |
Preclinical Drug(s) | [+] 2 Preclinical Drugs | + | ||||
1 | PHA-568487 | Drug Info | Preclinical | Cognitive impairment | [23] | |
2 | RMG-40083 | Drug Info | Preclinical | Schizophrenia | [1] | |
Mode of Action | [+] 6 Modes of Action | + | ||||
Inhibitor | [+] 9 Inhibitor drugs | + | ||||
1 | ALCURONIUM | Drug Info | [25] | |||
2 | CYTISINE | Drug Info | [27] | |||
3 | 3,8-dibromoboldine | Drug Info | [41] | |||
4 | 3-bromoboldine | Drug Info | [41] | |||
5 | CP-810123 | Drug Info | [47] | |||
6 | GCCSHPACAGNNQHIC* | Drug Info | [48] | |||
7 | GCCSNPVCHLEHSNLC* | Drug Info | [48] | |||
8 | PH-709829 | Drug Info | [51] | |||
9 | TOXIFERINE | Drug Info | [25] | |||
Binder | [+] 1 Binder drugs | + | ||||
1 | Ziprasidone | Drug Info | [1] | |||
Agonist | [+] 14 Agonist drugs | + | ||||
1 | AMG 386 | Drug Info | [26] | |||
2 | AQW-051 | Drug Info | [30] | |||
3 | GTS-21 | Drug Info | [31], [32] | |||
4 | R4996 | Drug Info | [26] | |||
5 | PHA-568487 | Drug Info | [40] | |||
6 | 4BP-TQS | Drug Info | [42] | |||
7 | A-582941 | Drug Info | [43] | |||
8 | AZD-6319 | Drug Info | [45] | |||
9 | EVP-4473 | Drug Info | [45] | |||
10 | JN-711 | Drug Info | [45] | |||
11 | PSAB-OFP | Drug Info | [53] | |||
12 | [125I]epibatidine | Drug Info | [45] | |||
13 | [3H]A-585539 | Drug Info | [54] | |||
14 | [3H]AZ11637326 | Drug Info | [55] | |||
Modulator | [+] 11 Modulator drugs | + | ||||
1 | EVP-6124 | Drug Info | [28] | |||
2 | ABT-126 | Drug Info | [29] | |||
3 | JNJ-39393406 | Drug Info | [33] | |||
4 | TC-6987 | Drug Info | [34] | |||
5 | AVL-3288 | Drug Info | [35] | |||
6 | BMS-933043 | Drug Info | [36] | |||
7 | BNC375 | Drug Info | [16] | |||
8 | AZD0328 | Drug Info | [38] | |||
9 | ABT-107 | Drug Info | [39] | |||
10 | JNJ-1930942 | Drug Info | [45] | |||
11 | PheTQS | Drug Info | [45] | |||
Antagonist | [+] 6 Antagonist drugs | + | ||||
1 | MEM-3454 | Drug Info | [1] | |||
2 | AZD-9684 | Drug Info | [37] | |||
3 | RMG-40083 | Drug Info | [1] | |||
4 | PNU-282987 | Drug Info | [1] | |||
5 | Barbituric acid derivative | Drug Info | [46] | |||
6 | [3H]methyllycaconitine | Drug Info | [45], [56], [57] | |||
Modulator (allosteric modulator) | [+] 4 Modulator (allosteric modulator) drugs | + | ||||
1 | A-867744 | Drug Info | [44] | |||
2 | LY2087101 | Drug Info | [49] | |||
3 | NS1738 | Drug Info | [50] | |||
4 | PNU-120596 | Drug Info | [52] |
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 Affiliated Biological Pathways | Top | |||||
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KEGG Pathway | [+] 5 KEGG Pathways | + | ||||
1 | Calcium signaling pathway | |||||
2 | Neuroactive ligand-receptor interaction | |||||
3 | Cholinergic synapse | |||||
4 | Nicotine addiction | |||||
5 | Chemical carcinogenesis | |||||
Panther Pathway | [+] 2 Panther Pathways | + | ||||
1 | Alzheimer disease-amyloid secretase pathway | |||||
2 | Nicotinic acetylcholine receptor signaling pathway | |||||
Reactome | [+] 1 Reactome Pathways | + | ||||
1 | Highly calcium permeable postsynaptic nicotinic acetylcholine receptors | |||||
WikiPathways | [+] 2 WikiPathways | + | ||||
1 | SIDS Susceptibility Pathways | |||||
2 | Neurotransmitter Receptor Binding And Downstream Transmission In The Postsynaptic Cell |
Target-Related Models and Studies | Top | |||||
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Target Validation |
References | Top | |||||
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REF 1 | The pipeline and future of drug development in schizophrenia. Mol Psychiatry. 2007 Oct;12(10):904-22. | |||||
REF 2 | 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: 341). | |||||
REF 3 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
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: 59). | |||||
REF 5 | Emerging anxiolytics. Expert Opin Emerg Drugs. 2007 Nov;12(4):541-54. | |||||
REF 6 | Emerging drugs in neuropathic pain. Expert Opin Emerg Drugs. 2007 Mar;12(1):113-26. | |||||
REF 7 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
REF 8 | ClinicalTrials.gov (NCT02004392) Study of the Safety and Clinical Effects of 2 Doses of EVP-6124 in Subjects With Alzheimer's Disease Who Complete Study EVP-6124-024 or EVP-6124-025. U.S. National Institutes of Health. | |||||
REF 9 | ClinicalTrials.gov (NCT01655680) A Study to Evaluate ABT-126 for the Treatment of Cognitive Deficits in Schizophrenia. U.S. National Institutes of Health. | |||||
REF 10 | 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: 7371). | |||||
REF 11 | ClinicalTrials.gov (NCT01474421) Safety and Efficacy of AQW051 in L-dopa Induced Dyskinesias in Patients With Parkinson's Disease. U.S. National Institutes of Health. | |||||
REF 12 | ClinicalTrials.gov (NCT02432066) Effects of GTS-21 on Smoking Behavior and Neurocognitive Functions. U.S. National Institutes of Health. | |||||
REF 13 | ClinicalTrials.gov (NCT01296087) TC-6987 for the Treatment of Mild to Moderate Asthma. U.S. National Institutes of Health. | |||||
REF 14 | ClinicalTrials.gov (NCT01851603) Phase I Study to Evaluate the Safety and Pharmacokinetics of Oral Doses of Anvylic-3288 in Healthy Subjects. U.S. National Institutes of Health. | |||||
REF 15 | ClinicalTrials.gov (NCT01605994) Multiple Ascending-Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of BMS-933043 in Healthy Subjects. U.S. National Institutes of Health. | |||||
REF 16 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
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 Roche. | |||||
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 800018349) | |||||
REF 20 | 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: 7697). | |||||
REF 21 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800018503) | |||||
REF 22 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800026401) | |||||
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 800018656) | |||||
REF 24 | 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: 3988). | |||||
REF 25 | 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. | |||||
REF 26 | Clinical pipeline report, company report or official report of Roche (2009). | |||||
REF 27 | 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. | |||||
REF 28 | 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. | |||||
REF 29 | 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. | |||||
REF 30 | 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. | |||||
REF 31 | 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. | |||||
REF 32 | Selective alpha7-nicotinic agonists normalize inhibition of auditory response in DBA mice. Psychopharmacology (Berl). 1998 Apr;136(4):320-7. | |||||
REF 33 | Allosteric alpha-7 nicotinic receptor modulation and P50 sensory gating in schizophrenia: a proof-of-mechanism study. Neuropharmacology. 2013 Jan;64:197-204. | |||||
REF 34 | ClinicalTrials.gov (NCT01293669) Glycemic Control, Safety and Tolerability of TC-6987 Monotherapy in Type 2 Diabetes Mellitus. U.S. National Institutes of Health. | |||||
REF 35 | Differential immediate and sustained memory enhancing effects of alpha7 nicotinic receptor agonists and allosteric modulators in rats. PLoS One. 2011;6(11):e27014. | |||||
REF 36 | Clinical pipeline report, company report or official report of Phrma.org Alzheimers 2012. | |||||
REF 37 | Blockade and activation of the human neuronal nicotinic acetylcholine receptors by atracurium and laudanosine. Anesthesiology. 2001 Apr;94(4):643-51. | |||||
REF 38 | Ultra-low exposure to -7 nicotinic acetylcholine receptor partial agonists elicits an improvement in cognition that corresponds with an increase in -7 receptor expression in rodents: implications for low dose clinical efficacy.Neuroscience.2011 Jul 14;186:76-87. | |||||
REF 39 | In vitro pharmacological characterization of a novel selective alpha7 neuronal nicotinic acetylcholine receptor agonist ABT-107. J Pharmacol Exp Ther. 2010 Sep 1;334(3):863-74. | |||||
REF 40 | Multiple species metabolism of PHA-568487, a selective alpha 7 nicotinic acetylcholine receptor agonist. Drug Metab Lett. 2010 Aug;4(3):162-72. | |||||
REF 41 | Aporphine metho salts as neuronal nicotinic acetylcholine receptor blockers. Bioorg Med Chem. 2007 May 15;15(10):3368-72. | |||||
REF 42 | Agonist activation of alpha7 nicotinic acetylcholine receptors via an allosteric transmembrane site. Proc Natl Acad Sci U S A. 2011 Apr 5;108(14):5867-72. | |||||
REF 43 | Broad-spectrum efficacy across cognitive domains by alpha7 nicotinic acetylcholine receptor agonism correlates with activation of ERK1/2 and CREB phosphorylation pathways. J Neurosci. 2007 Sep 26;27(39):10578-87. | |||||
REF 44 | In vitro pharmacological characterization of a novel allosteric modulator of alpha 7 neuronal acetylcholine receptor, 4-(5-(4-chlorophenyl)-2-methy... J Pharmacol Exp Ther. 2009 Jul;330(1):257-67. | |||||
REF 45 | 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. (Target id: 468). | |||||
REF 46 | Whiting PJ: The GABAA receptor gene family: new opportunities for drug development. Curr Opin Drug Discov Devel. 2003 Sep;6(5):648-57. | |||||
REF 47 | Discovery of 4-(5-methyloxazolo[4,5-b]pyridin-2-yl)-1,4-diazabicyclo[3.2.2]nonane (CP-810,123), a novel alpha 7 nicotinic acetylcholine receptor ag... J Med Chem. 2010 Feb 11;53(3):1222-37. | |||||
REF 48 | Neuronal nicotinic acetylcholine receptors: structural revelations, target identifications, and therapeutic inspirations. J Med Chem. 2005 Jul 28;48(15):4705-45. | |||||
REF 49 | Identification and pharmacological profile of a new class of selective nicotinic acetylcholine receptor potentiators. J Pharmacol Exp Ther. 2006 Sep;318(3):1108-17. | |||||
REF 50 | 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. | |||||
REF 51 | Discovery of N-[(3R,5R)-1-azabicyclo[3.2.1]oct-3-yl]furo[2,3-c]pyridine-5-carboxamide as an agonist of the alpha7 nicotinic acetylcholine receptor:... Bioorg Med Chem Lett. 2008 Jun 15;18(12):3611-5. | |||||
REF 52 | A novel positive allosteric modulator of the alpha7 neuronal nicotinic acetylcholine receptor: in vitro and in vivo characterization. J Neurosci. 2005 Apr 27;25(17):4396-405. | |||||
REF 53 | PSAB-OFP, a selective alpha 7 nicotinic receptor agonist, is also a potent agonist of the 5-HT3 receptor. Eur J Pharmacol. 2002 Oct 4;452(2):137-44. | |||||
REF 54 | [3H]A-585539 [(1S,4S)-2,2-dimethyl-5-(6-phenylpyridazin-3-yl)-5-aza-2-azoniabicyclo[2.2.1]heptane], a novel high-affinity alpha7 neuronal nicotinic... J Pharmacol Exp Ther. 2008 Jan;324(1):179-87. | |||||
REF 55 | In vitro binding characteristics of [3H]AZ11637326, a novel alpha7-selective neuronal nicotinic receptor agonist radioligand. Eur J Pharmacol. 2010 Oct 25;645(1-3):63-9. | |||||
REF 56 | Nicotine increases the expression of high affinity nerve growth factor receptors in both in vitro and in vivo. Life Sci. 2002 Feb 15;70(13):1543-54. | |||||
REF 57 | Experience of Black participants in the Lung Health Study smoking cessation intervention program. Nicotine Tob Res. 2001 Nov;3(4):375-82. |
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