Target Information
| Target General Information | Top | |||||
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| Target ID |
T73724
(Former ID: TTDR00164)
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| Target Name |
Neuronal acetylcholine receptor beta-4 (CHRNB4)
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| Synonyms |
CHRNB4; Beta-4 nAChR
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| Gene Name |
CHRNB4
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | 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.
Click to Show/Hide
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| BioChemical Class |
Neurotransmitter receptor
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| UniProt ID | ||||||
| Sequence |
MRRAPSLVLFFLVALCGRGNCRVANAEEKLMDDLLNKTRYNNLIRPATSSSQLISIKLQL
SLAQLISVNEREQIMTTNVWLKQEWTDYRLTWNSSRYEGVNILRIPAKRIWLPDIVLYNN ADGTYEVSVYTNLIVRSNGSVLWLPPAIYKSACKIEVKYFPFDQQNCTLKFRSWTYDHTE IDMVLMTPTASMDDFTPSGEWDIVALPGRRTVNPQDPSYVDVTYDFIIKRKPLFYTINLI IPCVLTTLLAILVFYLPSDCGEKMTLCISVLLALTFFLLLISKIVPPTSLDVPLIGKYLM FTMVLVTFSIVTSVCVLNVHHRSPSTHTMAPWVKRCFLHKLPTFLFMKRPGPDSSPARAF PPSKSCVTKPEATATSTSPSNFYGNSMYFVNPASAASKSPAGSTPVAIPRDFWLRSSGRF RQDVQEALEGVSFIAQHMKNDDEDQSVVEDWKYVAMVVDRLFLWVFMFVCVLGTVGLFLP PLFQTHAASEGPYAAQRD Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
| 1 | CYTISINE | Drug Info | Phase 3 | Tobacco dependence | [2] | |
| Discontinued Drug(s) | [+] 1 Discontinued Drugs | + | ||||
| 1 | SIB-1553A | Drug Info | Discontinued in Phase 2 | Alzheimer disease | [3] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Inhibitor | [+] 14 Inhibitor drugs | + | ||||
| 1 | CYTISINE | Drug Info | [1] | |||
| 2 | HOMOEPIBATIDINE | Drug Info | [5] | |||
| 3 | (2S,3S)-2-(m-Tolyl)-3,5,5-trimethylmorpholin-2-ol | Drug Info | [6] | |||
| 4 | (2S,3S)-2-Phenyl-3,5,5-trimethylmorpholin-2-ol | Drug Info | [6] | |||
| 5 | 15-nor-18-Methoxycornaridine | Drug Info | [7] | |||
| 6 | 18-Dimethylaminocoronaridine | Drug Info | [7] | |||
| 7 | 18-methoxycoronaridinate 2-Hydroxyethylamide | Drug Info | [7] | |||
| 8 | 18-methoxycoronaridinate 2-methoxyethylamide | Drug Info | [7] | |||
| 9 | 18-Methylaminocoronaridine | Drug Info | [7] | |||
| 10 | 2-Acetylaminoethyl 18-methoxycoronaridinate | Drug Info | [7] | |||
| 11 | 2-Hydroxyethyl 18-methoxycoronaridinate | Drug Info | [7] | |||
| 12 | 2-Methoxyethyl 18-methoxycoronaridinate | Drug Info | [7] | |||
| 13 | GCCSNPVCHLEHSNLC* | Drug Info | [8] | |||
| 14 | N,N-Dimethylaminoethyl 18-methoxycoronaridinate | Drug Info | [7] | |||
| Agonist | [+] 1 Agonist drugs | + | ||||
| 1 | SIB-1553A | Drug Info | [4] | |||
| 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 Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 2 KEGG Pathways | + | ||||
| 1 | Neuroactive ligand-receptor interaction | |||||
| 2 | Cholinergic synapse | |||||
| Panther Pathway | [+] 2 Panther Pathways | + | ||||
| 1 | Nicotinic acetylcholine receptor signaling pathway | |||||
| 2 | Nicotine pharmacodynamics pathway | |||||
| Reactome | [+] 3 Reactome Pathways | + | ||||
| 1 | Highly sodium permeable acetylcholine nicotinic receptors | |||||
| 2 | Highly calcium permeable postsynaptic nicotinic acetylcholine receptors | |||||
| 3 | Highly calcium permeable nicotinic acetylcholine receptors | |||||
| WikiPathways | [+] 3 WikiPathways | + | ||||
| 1 | SIDS Susceptibility Pathways | |||||
| 2 | Neurotransmitter Receptor Binding And Downstream Transmission In The Postsynaptic Cell | |||||
| 3 | Nicotine Activity on Chromaffin Cells | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Deconstructing cytisine: The syntheses of (+/-)-cyfusine and (+/-)-cyclopropylcyfusine, fused ring analogs of cytisine. Bioorg Med Chem Lett. 2008 Apr 1;18(7):2316-9. | |||||
| REF 2 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 3 | 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 4 | SIB-1553A, (+/-)-4-[[2-(1-methyl-2-pyrrolidinyl)ethyl]thio]phenol hydrochloride, a subtype-selective ligand for nicotinic acetylcholine receptors with putative cognitive-enhancing properties: effectson working and reference memory performances in aged rodents and nonhuman primates. J Pharmacol Exp Ther. 2001 Oct;299(1):297-306. | |||||
| REF 5 | Epibatidine isomers and analogues: structure-activity relationships. Bioorg Med Chem Lett. 2006 Nov 1;16(21):5493-7. | |||||
| REF 6 | Synthesis and characterization of in vitro and in vivo profiles of hydroxybupropion analogues: aids to smoking cessation. J Med Chem. 2010 Jun 24;53(12):4731-48. | |||||
| REF 7 | Synthesis and biological evaluation of 18-methoxycoronaridine congeners. Potential antiaddiction agents. J Med Chem. 2003 Jun 19;46(13):2716-30. | |||||
| REF 8 | Neuronal nicotinic acetylcholine receptors: structural revelations, target identifications, and therapeutic inspirations. J Med Chem. 2005 Jul 28;48(15):4705-45. | |||||
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