Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTTVAFQ)

• DTT Name: Neuronal acetylcholine receptor beta-4 (CHRNB4)
• Synonyms: CHRNB4; Beta-4 nAChR
• Gene Name: CHRNB4
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Neurotransmitter receptor
• UniProt ID: ACHB4_HUMAN
• TTD ID: T73724
• Sequence:
  MRRAPSLVLFFLVALCGRGNCRVANAEEKLMDDLLNKTRYNNLIRPATSSSQLISIKLQL
  SLAQLISVNEREQIMTTNVWLKQEWTDYRLTWNSSRYEGVNILRIPAKRIWLPDIVLYNN
  ADGTYEVSVYTNLIVRSNGSVLWLPPAIYKSACKIEVKYFPFDQQNCTLKFRSWTYDHTE
  IDMVLMTPTASMDDFTPSGEWDIVALPGRRTVNPQDPSYVDVTYDFIIKRKPLFYTINLI
  IPCVLTTLLAILVFYLPSDCGEKMTLCISVLLALTFFLLLISKIVPPTSLDVPLIGKYLM
  FTMVLVTFSIVTSVCVLNVHHRSPSTHTMAPWVKRCFLHKLPTFLFMKRPGPDSSPARAF
  PPSKSCVTKPEATATSTSPSNFYGNSMYFVNPASAASKSPAGSTPVAIPRDFWLRSSGRF
  RQDVQEALEGVSFIAQHMKNDDEDQSVVEDWKYVAMVVDRLFLWVFMFVCVLGTVGLFLP
  PLFQTHAASEGPYAAQRD
• 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.
• KEGG Pathway:
  Neuroactive ligand-receptor interaction (hsa04080)
  Cholinergic synapse (hsa04725)
• Reactome Pathway:
  Highly calcium permeable postsynaptic nicotinic acetylcholine receptors (R-HSA-629594)
  Highly calcium permeable nicotinic acetylcholine receptors (R-HSA-629597)
  Highly sodium permeable acetylcholine nicotinic receptors (R-HSA-629587)

Molecular Interaction Atlas (MIA) of This DTT

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CYTISINE	DMUF0BJ	Tobacco dependence	6C4A.2	Phase 3	[1]

2 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
SIB-1553A	DM7XC0U	Alzheimer disease	8A20	Discontinued in Phase 2	[2]
HOMOEPIBATIDINE	DMHP9WV	N. A.	N. A.	Terminated	[3]

12 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(2S,3S)-2-(m-Tolyl)-3,5,5-trimethylmorpholin-2-ol	DMDUI8R	Discovery agent	N.A.	Investigative	[4]
(2S,3S)-2-Phenyl-3,5,5-trimethylmorpholin-2-ol	DMDUGZS	Discovery agent	N.A.	Investigative	[4]
15-nor-18-Methoxycornaridine	DMDKFGX	Discovery agent	N.A.	Investigative	[5]
18-Dimethylaminocoronaridine	DM0JEQ6	Discovery agent	N.A.	Investigative	[5]
18-methoxycoronaridinate 2-Hydroxyethylamide	DMBG9Z3	Discovery agent	N.A.	Investigative	[5]
18-methoxycoronaridinate 2-methoxyethylamide	DMSBAC0	Discovery agent	N.A.	Investigative	[5]
18-Methylaminocoronaridine	DMOYC0U	Discovery agent	N.A.	Investigative	[5]
2-Acetylaminoethyl 18-methoxycoronaridinate	DM9ZOX4	Discovery agent	N.A.	Investigative	[5]
2-Hydroxyethyl 18-methoxycoronaridinate	DMT6APV	Discovery agent	N.A.	Investigative	[5]
2-Methoxyethyl 18-methoxycoronaridinate	DM6X8GN	Discovery agent	N.A.	Investigative	[5]
GCCSNPVCHLEHSNLC*	DMJ0ICN	Discovery agent	N.A.	Investigative	[6]
N,N-Dimethylaminoethyl 18-methoxycoronaridinate	DMWJ2PM	Discovery agent	N.A.	Investigative	[5]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Alzheimer's disease	8A00.0	Entorhinal cortex	8.30E-01	9.66E-03	0.06

References

• [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.
• [2] 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.
• [3] Epibatidine isomers and analogues: structure-activity relationships. Bioorg Med Chem Lett. 2006 Nov 1;16(21):5493-7.
• [4] 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.
• [5] Synthesis and biological evaluation of 18-methoxycoronaridine congeners. Potential antiaddiction agents. J Med Chem. 2003 Jun 19;46(13):2716-30.
• [6] Neuronal nicotinic acetylcholine receptors: structural revelations, target identifications, and therapeutic inspirations. J Med Chem. 2005 Jul 28;48(15):4705-45.