Target Information
Target General Infomation | |||||
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Target ID |
T34429
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Former ID |
TTDS00520
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Target Name |
Neuronal acetylcholine receptor protein, alpha-7 chain
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Gene Name |
CHRNA7
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Synonyms |
Alpha(7) nicotinic receptor; Alpha-7 nAChR; Alpha7 nAChR; Alpha7 nicotinic receptor; Nicotinic acetylcholine receptor alpha7; Nicotinic acetylcholine receptor subunit alpha 7; CHRNA7
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Target Type |
Successful
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Disease | Alzheimer disease; Schizophrenia [ICD9: 295, 331.0; ICD10: F20, G30] | ||||
Attention deficit hyperactivity disorder [ICD9: 314; ICD10: F90] | |||||
Alzheimer disease [ICD9: 331; ICD10: G30] | |||||
Anesthesia [ICD9: 338; ICD10: R20.0] | |||||
Asthma [ICD10: J45] | |||||
Cognitive disorders [ICD9: 290-294, 294.0, 780.09, 780.9, 780.93; ICD10: F01-F07, F04, F05, R41.3] | |||||
Central nervous system disease [ICD10: G00-G99] | |||||
Mild to moderate alzheimer disease; Schizophrenia [ICD9:331, 295; ICD10: G30, F20] | |||||
Neurological disease [ICD9: 338, 338.2, 410, 782.3,780; ICD10: I21, I22, R52, R52.1-R52.2, R60.9, G89] | |||||
Parkinson's disease [ICD9: 332; ICD10: G20] | |||||
Psychiatric disorder [ICD9: 290-319; ICD10: F01-F99] | |||||
Schizophrenia [ICD9: 295; ICD10: F20] | |||||
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.
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BioChemical Class |
Neurotransmitter receptor
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Target Validation |
T34429
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UniProt ID | |||||
Sequence |
MRCSPGGVWLALAASLLHVSLQGEFQRKLYKELVKNYNPLERPVANDSQPLTVYFSLSLL
QIMDVDEKNQVLTTNIWLQMSWTDHYLQWNVSEYPGVKTVRFPDGQIWKPDILLYNSADE RFDATFHTNVLVNSSGHCQYLPPGIFKSSCYIDVRWFPFDVQHCKLKFGSWSYGGWSLDL QMQEADISGYIPNGEWDLVGIPGKRSERFYECCKEPYPDVTFTVTMRRRTLYYGLNLLIP CVLISALALLVFLLPADSGEKISLGITVLLSLTVFMLLVAEIMPATSDSVPLIAQYFAST MIIVGLSVVVTVIVLQYHHHDPDGGKMPKWTRVILLNWCAWFLRMKRPGEDKVRPACQHK QRRCSLASVEMSAVAPPPASNGNLLYIGFRGLDGVHCVPTPDSGVVCGRMACSPTHDEHL LHGGQPPEGDPDLAKILEEVRYIANRFRCQDESEAVCSEWKFAACVVDRLCLMAFSVFTI ICTIGILMSAPNFVEAVSKDFA |
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Structure |
2MAW
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Drugs and Mode of Action | |||||
Drug(s) | ALCURONIUM | Drug Info | Approved | Anesthesia | [540355], [551871] |
TC-5280 | Drug Info | Approved | Schizophrenia | [536463] | |
EVP-6124 | Drug Info | Phase 3 | Mild to moderate alzheimer disease; Schizophrenia | [524557] | |
ABT-126 | Drug Info | Phase 2 | Mild to moderate alzheimer disease; Schizophrenia | [524000] | |
AQW-051 | Drug Info | Phase 2 | Alzheimer disease | [523693], [542393] | |
GTS-21 | Drug Info | Phase 2 | Parkinson's disease | [525179] | |
MEM-3454 | Drug Info | Phase 2 | Schizophrenia | [536463] | |
R3487 | Drug Info | Phase 2 | Alzheimer disease; Schizophrenia | [530352] | |
TC-6987 | Drug Info | Phase 2 | Asthma | [523358] | |
AVL-3288 | Drug Info | Phase 1 | Cognitive disorders | [524285] | |
BMS-933043 | Drug Info | Phase 1 | Psychiatric disorder | [523918] | |
JNJ-39393406 | Drug Info | Phase 1 | Cognitive disorders | [523838] | |
R4996 | Drug Info | Phase 1 | Neurological disease | [551602] | |
PHA-568487 | Drug Info | Preclinical | Cognitive disorders | [547709] | |
RMG-40083 | Drug Info | Preclinical | Schizophrenia | [536463] | |
AZD0328 | Drug Info | Discontinued in Phase 2 | Alzheimer disease | [542672], [547698] | |
ABT-107 | Drug Info | Discontinued in Phase 1 | Attention deficit hyperactivity disorder | [548535] | |
PNU-282987 | Drug Info | Terminated | Schizophrenia | [536463], [540603] | |
Inhibitor | 3,8-dibromoboldine | Drug Info | [528761] | ||
3-bromoboldine | Drug Info | [528761] | |||
ALCURONIUM | Drug Info | [528997] | |||
CP-810123 | Drug Info | [530609] | |||
CYTISINE | Drug Info | [527753] | |||
GCCSHPACAGNNQHIC* | Drug Info | [527644] | |||
GCCSNPVCHLEHSNLC* | Drug Info | [527644] | |||
PH-709829 | Drug Info | [529479] | |||
TOXIFERINE | Drug Info | [528997] | |||
Agonist | 4BP-TQS | Drug Info | [531407] | ||
A-582941 | Drug Info | [529066] | |||
AQW-051 | Drug Info | [532935] | |||
AZD-6319 | Drug Info | [543845] | |||
EVP-4473 | Drug Info | [543845] | |||
GTS-21 | Drug Info | [535029], [538103] | |||
JN-711 | Drug Info | [543845] | |||
PHA-568487 | Drug Info | [531041] | |||
PHA-709829 | Drug Info | [529479] | |||
PSAB-OFP | Drug Info | [526434] | |||
R3487 | Drug Info | [551607] | |||
R4996 | Drug Info | [551607] | |||
[3H]A-585539 | Drug Info | [529116] | |||
[3H]AZ11637326 | Drug Info | [531071] | |||
[3H]epibatidine | Drug Info | [543845] | |||
Modulator (allosteric modulator) | A-867744 | Drug Info | [530093] | ||
LY2087101 | Drug Info | [528221] | |||
NS1738 | Drug Info | [528946] | |||
PNU-120596 | Drug Info | [527539] | |||
Modulator | ABT-107 | Drug Info | [530943] | ||
ABT-126 | Drug Info | [551664] | |||
AVL-3288 | Drug Info | [531708] | |||
AZD0328 | Drug Info | ||||
BMS-933043 | Drug Info | [550057] | |||
EVP-6124 | Drug Info | [532624] | |||
JNJ-1930942 | Drug Info | [543845] | |||
JNJ-39393406 | Drug Info | [531960] | |||
PheTQS | Drug Info | [543845] | |||
TC-6987 | Drug Info | [523353] | |||
Antagonist | Barbituric acid derivative | Drug Info | [551407] | ||
Laudanosine | Drug Info | [535185] | |||
MEM-3454 | Drug Info | [536463] | |||
Methyllycaconitine | Drug Info | [535293], [535398] | |||
PNU-282987 | Drug Info | [536463] | |||
RMG-40083 | Drug Info | [536463] | |||
[3H]methyllycaconitine | Drug Info | [543845] | |||
Binder | TC-5280 | Drug Info | [536463] | ||
Pathways | |||||
KEGG Pathway | Calcium signaling pathway | ||||
Neuroactive ligand-receptor interaction | |||||
Cholinergic synapse | |||||
Nicotine addiction | |||||
Chemical carcinogenesis | |||||
PANTHER Pathway | Alzheimer disease-amyloid secretase pathway | ||||
Nicotinic acetylcholine receptor signaling pathway | |||||
Reactome | Highly calcium permeable postsynaptic nicotinic acetylcholine receptors | ||||
WikiPathways | SIDS Susceptibility Pathways | ||||
Neurotransmitter Receptor Binding And Downstream Transmission In The Postsynaptic Cell | |||||
References | |||||
Ref 523358 | ClinicalTrials.gov (NCT01296087) TC-6987 for the Treatment of Mild to Moderate Asthma. U.S. National Institutes of Health. | ||||
Ref 523693 | 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 523838 | ClinicalTrials.gov (NCT01556217) A Pharmacokinetic Study to Characterize JNJ-39393406 in the Cerebrospinal Fluid of Healthy Volunteers. U.S. National Institutes of Health. | ||||
Ref 523918 | 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 524000 | ClinicalTrials.gov (NCT01655680) A Study to Evaluate ABT-126 for the Treatment of Cognitive Deficits in Schizophrenia. U.S. National Institutes of Health. | ||||
Ref 524285 | 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 524557 | 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 525179 | ClinicalTrials.gov (NCT02432066) Effects of GTS-21 on Smoking Behavior and Neurocognitive Functions. U.S. National Institutes of Health. | ||||
Ref 530352 | Nicotinic receptors: allosteric transitions and therapeutic targets in the nervous system. Nat Rev Drug Discov. 2009 Sep;8(9):733-50. | ||||
Ref 536463 | The pipeline and future of drug development in schizophrenia. Mol Psychiatry. 2007 Oct;12(10):904-22. Epub 2007 Jul 31. | ||||
Ref 540355 | (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 540603 | (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 542393 | (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 542672 | (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 547698 | 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 547709 | 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 523353 | ClinicalTrials.gov (NCT01293669) Glycemic Control, Safety and Tolerability of TC-6987 Monotherapy in Type 2 Diabetes Mellitus. U.S. National Institutes of Health. | ||||
Ref 526434 | 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 527539 | 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 527644 | J Med Chem. 2005 Jul 28;48(15):4705-45.Neuronal nicotinic acetylcholine receptors: structural revelations, target identifications, and therapeutic inspirations. | ||||
Ref 527753 | Bioorg Med Chem Lett. 2005 Nov 15;15(22):4889-97.3,5-Bicyclic aryl piperidines: a novel class of alpha4beta2 neuronal nicotinic receptor partial agonists for smoking cessation. | ||||
Ref 528221 | Identification and pharmacological profile of a new class of selective nicotinic acetylcholine receptor potentiators. J Pharmacol Exp Ther. 2006 Sep;318(3):1108-17. Epub 2006 May 31. | ||||
Ref 528761 | Bioorg Med Chem. 2007 May 15;15(10):3368-72. Epub 2007 Mar 13.Aporphine metho salts as neuronal nicotinic acetylcholine receptor blockers. | ||||
Ref 528946 | 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. Epub 2007 Jul 11. | ||||
Ref 528997 | J Med Chem. 2007 Sep 20;50(19):4616-29. Epub 2007 Aug 28.Pharmacological characteristics and binding modes of caracurine V analogues and related compounds at the neuronal alpha7 nicotinic acetylcholine receptor. | ||||
Ref 529066 | 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 529116 | [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 receptor agonist: radioligand binding characterization to rat and human brain. J Pharmacol Exp Ther. 2008 Jan;324(1):179-87. Epub 2007 Oct 24. | ||||
Ref 529479 | Bioorg Med Chem Lett. 2008 Jun 15;18(12):3611-5. Epub 2008 May 1.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: in vitro and in vivo activity. | ||||
Ref 530093 | J Pharmacol Exp Ther. 2009 Jul;330(1):257-67. Epub 2009 Apr 23.In vitro pharmacological characterization of a novel allosteric modulator of alpha 7 neuronal acetylcholine receptor, 4-(5-(4-chlorophenyl)-2-methyl-3-propionyl-1H-pyrrol-1-yl)benzenesulfonamide (A-867744), exhibiting unique pharmacological profile. | ||||
Ref 530609 | J Med Chem. 2010 Feb 11;53(3):1222-37.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 agonist for the treatment of cognitive disorders in schizophrenia: synthesis, SAR development, and in vivo efficacy in cognition models. | ||||
Ref 530943 | 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 531041 | Multiple species metabolism of PHA-568487, a selective alpha 7 nicotinic acetylcholine receptor agonist. Drug Metab Lett. 2010 Aug;4(3):162-72. | ||||
Ref 531071 | 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 531407 | 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 531708 | Differential immediate and sustained memory enhancing effects of alpha7 nicotinic receptor agonists and allosteric modulators in rats. PLoS One. 2011;6(11):e27014. | ||||
Ref 531960 | Allosteric alpha-7 nicotinic receptor modulation and P50 sensory gating in schizophrenia: a proof-of-mechanism study. Neuropharmacology. 2013 Jan;64:197-204. | ||||
Ref 532624 | 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 532935 | 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 535029 | 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 535185 | Blockade and activation of the human neuronal nicotinic acetylcholine receptors by atracurium and laudanosine. Anesthesiology. 2001 Apr;94(4):643-51. | ||||
Ref 535293 | Experience of Black participants in the Lung Health Study smoking cessation intervention program. Nicotine Tob Res. 2001 Nov;3(4):375-82. | ||||
Ref 535398 | 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 536463 | The pipeline and future of drug development in schizophrenia. Mol Psychiatry. 2007 Oct;12(10):904-22. Epub 2007 Jul 31. | ||||
Ref 538103 | Selective alpha7-nicotinic agonists normalize inhibition of auditory response in DBA mice. Psychopharmacology (Berl). 1998 Apr;136(4):320-7. | ||||
Ref 543845 | (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). |
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