| Target
Information |
| Name | Neuronal acetylcholine receptor protein, alpha-7 chain |
| Type of target | Successful target |
| Synonyms | Alpha(7) nicotinic receptor |
| Alpha-7 nAChR |
| Alpha7 nAChR |
| Alpha7 nicotinic receptor |
| Nicotinic acetylcholine receptor alpha7 |
| Nicotinic acetylcholine receptor subunit alpha 7 |
| Disease | Alzheimer's disease
[ICD9: 331.0 ICD10: G30] | [1][2] |
Analgesics
[ICD9: 338 ICD10: R52] | [3] |
Drug dependence
[ICD9: 303-304 ICD10: F10.2-F19.2] | [4] |
| Neuropsychiatric disorders | [4] |
Pain
[ICD9: 338,780 ICD10: R52, G89] | [3] |
Schizophrenia
[ICD9: 295 ICD10: F20] | [4] |
| Drug(s) | TC-5280 |  | Launched | Schizophrenia | [5] |
| EVP-6124 | | Phase II | Mild to moderate Alzheimer's disease | |
| EVP-6124 | | Phase II | Schizophrenia | |
| MEM-3454 | | Phase II | Schizophrenia | [5] |
| R3487 | | Phase II | Alzheimer's disease, schizophrenia | [6] |
| PNU-282987 | | Discontinued | Schizophrenia | [5] |
| R4996 | | Suspended in Phase I | Alzheimer's disease | [6] |
| RMG-40083 | | Preclinical | Schizophrenia | [5] |
| TC-1698 | | Preclinical | Schizophrenia | [5] |
| BioChemical Class | Ion transport |
| Pathway | Calcium signaling pathway |
| UniProt ID | P36544 |
| 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. |
| Sequence | MRCSPGGVWLALAASLLHVSLQGEFQRKLYKELVKNYNPLERPVANDSQPLTVYFSLSLL
QIMDVDEKNQVLTTNIWLQMSWTDHYLQWNVSEYPGVKTVRFPDGQIWKPDILLYNSADE
RFDATFHTNVLVNSSGHCQYLPPGIFKSSCYIDVRWFPFDVQHCKLKFGSWSYGGWSLDL
QMQEADISGYIPNGEWDLVGIPGKRSERFYECCKEPYPDVTFTVTMRRRTLYYGLNLLIP
CVLISALALLVFLLPADSGEKISLGITVLLSLTVFMLLVAEIMPATSDSVPLIAQYFAST
MIIVGLSVVVTVIVLQYHHHDPDGGKMPKWTRVILLNWCAWFLRMKRPGEDKVRPACQHK
QRRCSLASVEMSAVAPPPASNGNLLYIGFRGLDGVHCVPTPDSGVVCGRMACSPTHDEHL
LHGGQPPEGDPDLAKILEEVRYIANRFRCQDESEAVCSEWKFAACVVDRLCLMAFSVFTI
ICTIGILMSAPNFVEAVSKDFA
|
| Target Validation | Click to Find Target Validation Information. |
| Inhibitor | 3,8-dibromoboldine | | [7] |
| 3-bromoboldine | | [7] |
| ALCURONIUM | | [8] |
| CP-810123 | | [9] |
| CYTISINE | | [10] |
| GCCSHPACAGNNQHIC* | | [11] |
| GCCSNPVCHLEHSNLC* | | [11] |
| N-methyllaurotetanine methiodide | | [7] |
| PH-709829 | | [12] |
| PHA-543613 | | [12] |
| TOXIFERINE | | [8] |
| boldine methiodide | | [7] |
| glaucine methiodide | | [7] |
| Agonist | GTS-21 | | [2][13] |
| R3487 | | [6] |
| R4996 | | [6] |
| Antagonist | Barbital | | [14] |
| Barbituric acid derivative | | [14] |
| Laudanosine | | [15] |
| MEM-3454 | | [5] |
| Methyllycaconitine | | [1][16] |
| PNU-282987 | | [5] |
| RMG-40083 | | [5] |
| Binder | TC-1698 | | [5] |
| TC-5280 | | [5] |
| Cross References |
3D Structure
Related Literature
On-Line
Medical Dictionary |
| Ref 1 | 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. To Reference |
| Ref 2 | 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. To Reference |
| Ref 3 | Challenges in Analgesic Drug Development. Clin Pharmacol Ther. 2009 Aug 12. To Reference |
| Ref 4 | Rats exhibiting acute behavioural tolerance to nicotine have more [125I]alpha-bungarotoxin binding sites in brain than rats not exhibiting tolerance. Behav Brain Res. 2000 Aug;113(1-2):105-15. To Reference |
| Ref 5 | The pipeline and future of drug development in schizophrenia. Mol Psychiatry. 2007 Oct;12(10):904-22. Epub 2007 Jul 31. To Reference |
| Ref 6 | Roche. Product Development Pipeline. July 29 2009. To Reference |
| Ref 7 | Bioorg Med Chem. 2007 May 15;15(10):3368-72. Epub 2007 Mar 13.Aporphine metho salts as neuronal nicotinic acetylcholine receptor blockers. To Reference |
| Ref 8 | 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. To Reference |
| Ref 9 | 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. To Reference |
| Ref 10 | 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. To Reference |
| Ref 11 | J Med Chem. 2005 Jul 28;48(15):4705-45.Neuronal nicotinic acetylcholine receptors: structural revelations, target identifications, and therapeutic inspirations. To Reference |
| Ref 12 | 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. To Reference |
| Ref 13 | Selective alpha7-nicotinic agonists normalize inhibition of auditory response in DBA mice. Psychopharmacology (Berl). 1998 Apr;136(4):320-7. To Reference |
| Ref 14 | Whiting PJ: The GABAA receptor gene family: new opportunities for drug development. Curr Opin Drug Discov Devel. 2003 Sep;6(5):648-57. To Reference |
| Ref 15 | Blockade and activation of the human neuronal nicotinic acetylcholine receptors by atracurium and laudanosine. Anesthesiology. 2001 Apr;94(4):643-51. To Reference |
| Ref 16 | Experience of Black participants in the Lung Health Study smoking cessation intervention program. Nicotine Tob Res. 2001 Nov;3(4):375-82. To Reference |
