Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTYEG6Q)

• DTT Name: Muscarinic acetylcholine receptor M2 (CHRM2)
• Synonyms: M2 receptor; CHRM2
• Gene Name: CHRM2
• DTT Type: Successful target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: ACM2_HUMAN
• TTD ID: T46185
• Sequence:
  MNNSTNSSNNSLALTSPYKTFEVVFIVLVAGSLSLVTIIGNILVMVSIKVNRHLQTVNNY
  FLFSLACADLIIGVFSMNLYTLYTVIGYWPLGPVVCDLWLALDYVVSNASVMNLLIISFD
  RYFCVTKPLTYPVKRTTKMAGMMIAAAWVLSFILWAPAILFWQFIVGVRTVEDGECYIQF
  FSNAAVTFGTAIAAFYLPVIIMTVLYWHISRASKSRIKKDKKEPVANQDPVSPSLVQGRI
  VKPNNNNMPSSDDGLEHNKIQNGKAPRDPVTENCVQGEEKESSNDSTSVSAVASNMRDDE
  ITQDENTVSTSLGHSKDENSKQTCIRIGTKTPKSDSCTPTNTTVEVVGSSGQNGDEKQNI
  VARKIVKMTKQPAKKKPPPSREKKVTRTILAILLAFIITWAPYNVMVLINTFCAPCIPNT
  VWTIGYWLCYINSTINPACYALCNATFKKTFKHLLMCHYKNIGATR
• Function: The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is adenylate cyclase inhibition. Signaling promotes phospholipase C activity, leading to the release of inositol trisphosphate (IP3); this then triggers calcium ion release into the cytosol.
• KEGG Pathway:
  Calcium signaling pathway (hsa04020)
  cAMP signaling pathway (hsa04024)
  Neuroactive ligand-receptor interaction (hsa04080)
  PI3K-Akt signaling pathway (hsa04151)
  Cholinergic synapse (hsa04725)
  Regulation of actin cytoskeleton (hsa04810)
• Reactome Pathway:
  G alpha (i) signalling events (R-HSA-418594)
  Muscarinic acetylcholine receptors (R-HSA-390648)

Molecular Interaction Atlas (MIA) of This DTT

5 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ACECLIDINE	DMOLNCZ	Glaucoma/ocular hypertension	9C61	Approved	[2]
Gallamine Triethiodide	DMPO0MS	Stabilize muscle contraction	FB3Z	Approved	[3]
Methacholine Chloride	DMGS4QH	Asthma	CA23	Approved	[4]
Methylscopolamine	DM5VWOB	Peptic ulcer	DA61	Approved	[5]
SMT-D002	DM1I93C	Seborrhea	ED91.2	Approved	[6]

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
FP-1097	DMC1F2T	Urinary incontinence	MF50.2	Phase 2	[7]

9 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Otenzepad	DMRXHAC	Heart failure	BD10-BD13	Discontinued in Phase 2	[8]
PSD-506	DMT0KB1	Overactive bladder	GC50.0	Discontinued in Phase 2	[9]
SCH-211803	DM92E0W	Parkinson disease	8A00.0	Discontinued in Phase 1	[10]
Alvameline	DMLN0Y5	Alzheimer disease	8A20	Terminated	[11]
AQ-RA-741	DMPMW03	Cardiovascular disease	BA00-BE2Z	Terminated	[12]
BIBN-140	DM019Y7	Alzheimer disease	8A20	Terminated	[13]
BIBN-99	DMZTPCX	Alzheimer disease	8A20	Terminated	[14]
HIMBACINE	DMGAKD8	N. A.	N. A.	Terminated	[15]
Sch-57790	DMGCYPE	Alzheimer disease	8A20	Terminated	[16]

37 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(R)-4-[2-[3-(4-methoxy-benzoylamino)-benzyl]-piperidin-1-ylmethyl]piperidine-1-carboxylic acid amide (Ro-320-6206)	DMRVOLN	Discovery agent	N.A.	Investigative	[17]
1'-Benzyl-3-phenyl-[3,4']bipiperidinyl-2,6-dione	DMMNH4K	Discovery agent	N.A.	Investigative	[18]
1,1-diphenyl-2-(3-tropanyl)ethanol	DMZDUSA	Discovery agent	N.A.	Investigative	[19]
1-Methyl-1-(4-pyrrolidin-1-yl-but-2-ynyl)-urea	DM9KCXI	Discovery agent	N.A.	Investigative	[20]
2,8-Dimethyl-1-oxa-8-aza-spiro[4.5]decan-3-one	DMAKZ43	Discovery agent	N.A.	Investigative	[21]
2-(4-Diethylamino-but-2-ynyl)-isoindole-1,3-dione	DM823CD	Discovery agent	N.A.	Investigative	[22]
2-Methyl-6-pyrrolidin-1-yl-hex-4-ynal oxime	DM8EV4A	Discovery agent	N.A.	Investigative	[23]
3-(3-benzylamino)-piperidin-2-one	DMYN6Z9	Discovery agent	N.A.	Investigative	[24]
3-Methyl-7-pyrrolidin-1-yl-hept-5-yn-2-one	DME81U3	Discovery agent	N.A.	Investigative	[23]
3-Tetrazol-2-yl-1-aza-bicyclo[2.2.2]octane	DMIH6JU	Discovery agent	N.A.	Investigative	[25]
4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one	DMM9X0G	Discovery agent	N.A.	Investigative	[26]
6-Dimethylamino-2-methyl-hex-4-ynal oxime	DML2AC1	Discovery agent	N.A.	Investigative	[23]
7-Dimethylamino-3-methyl-hept-5-yn-2-one	DMDY2PQ	Discovery agent	N.A.	Investigative	[23]
7-Dimethylamino-hept-5-yn-2-one	DMH782V	Discovery agent	N.A.	Investigative	[23]
7-Pyrrolidin-1-yl-hept-5-yn-2-one	DMQJ26K	Discovery agent	N.A.	Investigative	[23]
A-987306	DMU34BK	Discovery agent	N.A.	Investigative	[27]
Acetic acid 8-aza-bicyclo[3.2.1]oct-6-yl ester	DMVEH40	Discovery agent	N.A.	Investigative	[4]
AF-DX-384	DMNY8H7	Discovery agent	N.A.	Investigative	[28]
Benzoic acid 8-aza-bicyclo[3.2.1]oct-6-yl ester	DM6T8YM	Discovery agent	N.A.	Investigative	[29]
BRL-55473	DMEMZ6Q	Discovery agent	N.A.	Investigative	[30]
CARAMIPEN	DMJFPA9	Discovery agent	N.A.	Investigative	[31]
CMI-1145	DMYPG01	Discovery agent	N.A.	Investigative	[32]
CMI-936	DMT9YKG	Discovery agent	N.A.	Investigative	[32]
FLUMEZAPINE	DMW0HOG	Discovery agent	N.A.	Investigative	[33]
FM1-10	DM5782Z	Discovery agent	N.A.	Investigative	[34]
FM1-43	DMAP8VY	Discovery agent	N.A.	Investigative	[34]
GNF-PF-5618	DMT8VUS	Discovery agent	N.A.	Investigative	[35]
Green tea	DMQHJTF	Discovery agent	N.A.	Investigative	[32]
ISOCLOZAPINE	DM52CPU	Discovery agent	N.A.	Investigative	[36]
ISOLOXAPINE	DMH1BN4	Discovery agent	N.A.	Investigative	[37]
METHOCTRAMINE	DMH2CKX	Discovery agent	N.A.	Investigative	[27]
N-(4-Dimethylamino-but-2-ynyl)-N-methyl-acetamide	DMB3E7H	Discovery agent	N.A.	Investigative	[23]
N-methoxyquinuclidine-3-carboximidoyl chloride	DMMB3PG	Discovery agent	N.A.	Investigative	[30]
N-methoxyquinuclidine-3-carboximidoyl fluoride	DMF8IA6	Discovery agent	N.A.	Investigative	[30]
Propionic acid 8-aza-bicyclo[3.2.1]oct-6-yl ester	DMO325J	Discovery agent	N.A.	Investigative	[29]
PTAC	DMEJ6SK	Discovery agent	N.A.	Investigative	[38]
SULFOARECOLINE	DM8KYUE	Discovery agent	N.A.	Investigative	[39]

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	4.61E-07	-0.59	-0.73
Asthma	CA23	Nasal and bronchial airway	4.59E-01	-0.02	-0.07
Parkinson's disease	8A00.0	Substantia nigra tissue	5.59E-01	0.19	0.41
Schizophrenia	6A20	Pre-frontal cortex	8.42E-02	-0.38	-0.24
Schizophrenia	6A20	Superior temporal cortex	2.55E-01	0.14	0.37

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