Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTF4E0J)

• DTT Name: Neuronal acetylcholine receptor alpha-2 (CHRNA2)
• Synonyms: CHRNA2
• Gene Name: CHRNA2
• DTT Type: Successful target; [1]
• BioChemical Class: Neurotransmitter receptor
• UniProt ID: ACHA2_HUMAN
• TTD ID: T55815
• Sequence:
  MGPSCPVFLSFTKLSLWWLLLTPAGGEEAKRPPPRAPGDPLSSPSPTALPQGGSHTETED
  RLFKHLFRGYNRWARPVPNTSDVVIVRFGLSIAQLIDVDEKNQMMTTNVWLKQEWSDYKL
  RWNPTDFGNITSLRVPSEMIWIPDIVLYNNADGEFAVTHMTKAHLFSTGTVHWVPPAIYK
  SSCSIDVTFFPFDQQNCKMKFGSWTYDKAKIDLEQMEQTVDLKDYWESGEWAIVNATGTY
  NSKKYDCCAEIYPDVTYAFVIRRLPLFYTINLIIPCLLISCLTVLVFYLPSDCGEKITLC
  ISVLLSLTVFLLLITEIIPSTSLVIPLIGEYLLFTMIFVTLSIVITVFVLNVHHRSPSTH
  TMPHWVRGALLGCVPRWLLMNRPPPPVELCHPLRLKLSPSYHWLESNVDAEEREVVVEEE
  DRWACAGHVAPSVGTLCSHGHLHSGASGPKAEALLQEGELLLSPHMQKALEGVHYIADHL
  RSEDADSSVKEDWKYVAMVIDRIFLWLFIIVCFLGTIGLFLPPFLAGMI
• 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)
• Reactome Pathway:
  Highly calcium permeable nicotinic acetylcholine receptors (R-HSA-629597)
  Highly calcium permeable postsynaptic nicotinic acetylcholine receptors (R-HSA-629594)

Molecular Interaction Atlas (MIA) of This DTT

8 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Carbachol	DMX9K8F	Glaucoma/ocular hypertension	9C61	Approved	[1]
Cisatracurium	DMUZPJ5	Muscle spasm	MB47.3	Approved	[2]
Levallorphan	DMCOLUP	Narcotic depression	6A7Z	Approved	[1]
Mivacurium	DM473VD	Anaesthesia	9A78.6	Approved	[2]
Pipecuronium	DM5F84A	Spasm	MB47.3	Approved	[1]
Rocuronium	DMY9BMK	Muscle spasm	MB47.3	Approved	[2]
Tubocurarine	DMBZIVP	Anaesthesia	9A78.6	Approved	[2]
Vecuronium	DMP0UK2	Spasm	MB47.3	Approved	[2]

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	[3]

11 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(S)-3-(azetidin-2-ylmethoxy)-2-fluoropyridine	DMB9CQL	Discovery agent	N.A.	Investigative	[4]
1,1-Dimethyl-4-phenyl-piperazin-1-ium iodide	DM9XTY7	Discovery agent	N.A.	Investigative	[5]
1-(piperidin-3-ylmethyl)pyridin-2(1H)-one	DMVRN0I	Discovery agent	N.A.	Investigative	[3]
1-(piperidin-4-ylmethyl)pyridin-2(1H)-one	DMKQZB7	Discovery agent	N.A.	Investigative	[3]
2-Pyridin-3-yl-7-aza-bicyclo[2.2.1]heptane	DM7RUNT	Discovery agent	N.A.	Investigative	[6]
3-((S)-Azetidin-2-yloxy)-5-iodo-pyridine	DMZU74I	Discovery agent	N.A.	Investigative	[5]
5-(1-Methyl-pyrrolidin-2-yl)-2-phenethyl-pyridine	DMMSK9W	Discovery agent	N.A.	Investigative	[7]
CHOLINE	DM5D9YK	Insomnia	7A00-7A0Z	Investigative	[5]
LY2087101	DMIS82X	Discovery agent	N.A.	Investigative	[8]
[125I]epibatidine	DMZWQH3	Discovery agent	N.A.	Investigative	[9]
[3H]cytisine	DMVLRHW	Discovery agent	N.A.	Investigative	[9]

References

• [1] Synergy between pairs of competitive antagonists at adult human muscle acetylcholine receptors. Anesth Analg. 2008 Aug;107(2):525-33.
• [2] Pharmacological characteristics of the inhibition of nondepolarizing neuromuscular blocking agents at human adult muscle nicotinic acetylcholine receptor. Anesthesiology. 2009 Jun;110(6):1244-52.
• [3] Synthesis and pharmacological evaluation of novel 9- and 10-substituted cytisine derivatives. Nicotinic ligands of enhanced subtype selectivity. J Med Chem. 2006 May 4;49(9):2673-6.
• [4] Synthesis and biological evaluation of novel carbon-11 labeled pyridyl ethers: candidate ligands for in vivo imaging of alpha4beta2 nicotinic acety... Bioorg Med Chem. 2009 Jul 1;17(13):4367-77.
• [5] Pharmacology of the agonist binding sites of rat neuronal nicotinic receptor subtypes expressed in HEK 293 cells. Bioorg Med Chem Lett. 2004 Apr 19;14(8):1845-8.
• [6] Epibatidine structure-activity relationships. Bioorg Med Chem Lett. 2004 Apr 19;14(8):1889-96.
• [7] 6-(2-Phenylethyl)nicotine: a novel nicotinic cholinergic receptor ligand. Bioorg Med Chem Lett. 2005 Jul 1;15(13):3237-40.
• [8] Identification and pharmacological profile of a new class of selective nicotinic acetylcholine receptor potentiators. J Pharmacol Exp Ther. 2006 Sep;318(3):1108-17.
• [9] 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: 463).