Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTQ13Z5)

• DTT Name: Muscarinic acetylcholine receptor M3 (CHRM3)
• Synonyms: M3 receptor; CHRM3
• Gene Name: CHRM3
• DTT Type: Successful target; [1]
• Related Disease:
  Asthma [ICD-11: CA23]
  Chronic obstructive pulmonary disease [ICD-11: CA22]
  Functional bladder disorder [ICD-11: GC50]
  Glaucoma [ICD-11: 9C61]
  Nausea/vomiting [ICD-11: MD90]
  Peptic ulcer [ICD-11: DA61]
  Respiratory system disease [ICD-11: CB40-CB7Z]
  Sebaceous gland disorder [ICD-11: ED91]
  Sjogren syndrome [ICD-11: 4A43]
  Tonus and reflex abnormality [ICD-11: MB47]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: ACM3_HUMAN
• TTD ID: T67684
• Sequence:
  MTLHNNSTTSPLFPNISSSWIHSPSDAGLPPGTVTHFGSYNVSRAAGNFSSPDGTTDDPL
  GGHTVWQVVFIAFLTGILALVTIIGNILVIVSFKVNKQLKTVNNYFLLSLACADLIIGVI
  SMNLFTTYIIMNRWALGNLACDLWLAIDYVASNASVMNLLVISFDRYFSITRPLTYRAKR
  TTKRAGVMIGLAWVISFVLWAPAILFWQYFVGKRTVPPGECFIQFLSEPTITFGTAIAAF
  YMPVTIMTILYWRIYKETEKRTKELAGLQASGTEAETENFVHPTGSSRSCSSYELQQQSM
  KRSNRRKYGRCHFWFTTKSWKPSSEQMDQDHSSSDSWNNNDAAASLENSASSDEEDIGSE
  TRAIYSIVLKLPGHSTILNSTKLPSSDNLQVPEEELGMVDLERKADKLQAQKSVDDGGSF
  PKSFSKLPIQLESAVDTAKTSDVNSSVGKSTATLPLSFKEATLAKRFALKTRSQITKRKR
  MSLVKEKKAAQTLSAILLAFIITWTPYNIMVLVNTFCDSCIPKTFWNLGYWLCYINSTVN
  PVCYALCNKTFRTTFKMLLLCQCDKKKRRKQQYQQRQSVIFHKRAPEQAL
• 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 Pi turnover.
• KEGG Pathway:
  Calcium signaling pathway (hsa04020)
  Neuroactive ligand-receptor interaction (hsa04080)
  Cholinergic synapse (hsa04725)
  Regulation of actin cytoskeleton (hsa04810)
  Insulin secretion (hsa04911)
  Salivary secretion (hsa04970)
  Gastric acid secretion (hsa04971)
  Pancreatic secretion (hsa04972)
• Reactome Pathway:
  Acetylcholine regulates insulin secretion (R-HSA-399997)
  G alpha (q) signalling events (R-HSA-416476)
  Muscarinic acetylcholine receptors (R-HSA-390648)

Molecular Interaction Atlas (MIA) of This DTT

13 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ACECLIDINE	DMOLNCZ	Glaucoma/ocular hypertension	9C61	Approved	[2]
Cevimeline	DMWSMND	Sjogren syndrome	4A43.20	Approved	[3]
Darifenacin	DMWXLYZ	Overactive bladder	GC50.0	Approved	[4], [5]
Ipratropium	DMFQ320	Obstructive lung disease	CA22.Z	Approved	[6]
LAS-34273	DMSQ1JV	Chronic obstructive pulmonary disease	CA22	Approved	[7]
Methacholine Chloride	DMGS4QH	Asthma	CA23	Approved	[8]
Methscopolamine bromide	DMHP8FI	Nausea and vomiting	MD90	Approved	[9]
Methylscopolamine	DM5VWOB	Peptic ulcer	DA61	Approved	[10]
SMT-D002	DM1I93C	Seborrhea	ED91.2	Approved	[11]
Solifenacin	DMG592Q	Overactive bladder	GC50.0	Approved	[12]
Succinylcholine	DM2ET1M	Spasm	MB47.3	Approved	[13], [14]
Tiotropium	DMFDC0Q	Chronic obstructive pulmonary disease	CA22	Approved	[1], [15]
Tolterodine	DMSHPW8	Overactive bladder	GC50.0	Approved	[16], [17]

3 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tarafenacin	DMDB4EJ	Overactive bladder	GC50.0	Phase 2	[18]
TRN-157	DM64NYP	Chronic obstructive pulmonary disease	CA22	Phase 2	[19]
CHF 5407	DMSDNU1	Chronic obstructive pulmonary disease	CA22	Phase 1	[20]

4 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Zamifenacin	DM51FVE	Urinary incontinence	MF50.2	Discontinued in Phase 3	[21]
PSD-506	DMT0KB1	Overactive bladder	GC50.0	Discontinued in Phase 2	[22]
Revatropate	DMT5VXF	Chronic obstructive pulmonary disease	CA22	Discontinued in Phase 1	[23]
Alvameline	DMLN0Y5	Alzheimer disease	8A20	Terminated	[24]

72 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
1'-Benzyl-3-phenyl-[3,4']bipiperidinyl-2,6-dione	DMMNH4K	Discovery agent	N.A.	Investigative	[25]
1,1-diphenyl-2-(3-tropanyl)ethanol	DMZDUSA	Discovery agent	N.A.	Investigative	[26]
1-Methyl-1-(4-pyrrolidin-1-yl-but-2-ynyl)-urea	DM9KCXI	Discovery agent	N.A.	Investigative	[27]
2,8-Dimethyl-1-oxa-8-aza-spiro[4.5]decan-3-one	DMAKZ43	Discovery agent	N.A.	Investigative	[28]
2-Methyl-6-pyrrolidin-1-yl-hex-4-ynal oxime	DM8EV4A	Discovery agent	N.A.	Investigative	[29]
3-(1-carbamoyl-1,1-diphenylmethyl)-1-(4-methoxyphenylethyl)pyrrolidine (APP)	DMOMSTN	Discovery agent	N.A.	Investigative	[16]
3-(3-benzylamino)-piperidin-2-one	DMYN6Z9	Discovery agent	N.A.	Investigative	[30]
3-Methyl-7-pyrrolidin-1-yl-hept-5-yn-2-one	DME81U3	Discovery agent	N.A.	Investigative	[29]
3-Tetrazol-2-yl-1-aza-bicyclo[2.2.2]octane	DMIH6JU	Discovery agent	N.A.	Investigative	[31]
4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one	DMM9X0G	Discovery agent	N.A.	Investigative	[32]
4-DAMP	DMZIUQ2	Discovery agent	N.A.	Investigative	[33], [34]
6-Dimethylamino-2-methyl-hex-4-ynal oxime	DML2AC1	Discovery agent	N.A.	Investigative	[29]
7-Dimethylamino-3-methyl-hept-5-yn-2-one	DMDY2PQ	Discovery agent	N.A.	Investigative	[29]
7-Dimethylamino-hept-5-yn-2-one	DMH782V	Discovery agent	N.A.	Investigative	[29]
7-Pyrrolidin-1-yl-hept-5-yn-2-one	DMQJ26K	Discovery agent	N.A.	Investigative	[29]
A-987306	DMU34BK	Discovery agent	N.A.	Investigative	[35]
Acetic acid 8-aza-bicyclo[3.2.1]oct-6-yl ester	DMVEH40	Discovery agent	N.A.	Investigative	[36]
AE-9C90CB	DMANEH2	Overactive bladder	GC50.0	Investigative	[19]
arecaidine propargyl ester	DMSA6IY	Discovery agent	N.A.	Investigative	[37]
Benzoic acid 8-aza-bicyclo[3.2.1]oct-6-yl ester	DM6T8YM	Discovery agent	N.A.	Investigative	[38]
BRL-55473	DMEMZ6Q	Discovery agent	N.A.	Investigative	[39]
brucine	DM50RUD	Discovery agent	N.A.	Investigative	[40]
Cremastrine	DMLJOGK	Discovery agent	N.A.	Investigative	[41]
DAU-5750	DMT14A7	Discovery agent	N.A.	Investigative	[42]
DAU-5884	DMEZVGK	Discovery agent	N.A.	Investigative	[43]
FLUMEZAPINE	DMW0HOG	Discovery agent	N.A.	Investigative	[44]
FM1-10	DM5782Z	Discovery agent	N.A.	Investigative	[45]
FM1-43	DMAP8VY	Discovery agent	N.A.	Investigative	[45]
furtrethonium	DM4M3C8	Discovery agent	N.A.	Investigative	[37]
GNF-PF-5618	DMT8VUS	Discovery agent	N.A.	Investigative	[46]
Go7874	DMS91OR	Discovery agent	N.A.	Investigative	[47]
guanylpirenzepine	DMOUQLB	Discovery agent	N.A.	Investigative	[48]
hexahydrodifenidol	DMH25OD	Discovery agent	N.A.	Investigative	[49]
hexahydrosiladifenidol	DM6UAV7	Discovery agent	N.A.	Investigative	[49]
ISOCLOZAPINE	DM52CPU	Discovery agent	N.A.	Investigative	[50]
ISOLOXAPINE	DMH1BN4	Discovery agent	N.A.	Investigative	[51]
J-104135	DMAEQS9	Chronic obstructive pulmonary disease	CA22	Investigative	[19]
lithocholylcholine	DME76CQ	Discovery agent	N.A.	Investigative	[52]
McN-A-343	DML3AZG	Discovery agent	N.A.	Investigative	[53]
methylfurmethide	DMZ318I	Discovery agent	N.A.	Investigative	[37]
ML381	DMKCIP0	Discovery agent	N.A.	Investigative	[54]
N-(4-Dimethylamino-but-2-ynyl)-N-methyl-acetamide	DMB3E7H	Discovery agent	N.A.	Investigative	[29]
N-benzyl brucine	DMOQMEU	Discovery agent	N.A.	Investigative	[40]
N-chloromethyl-brucine	DM6VEON	Discovery agent	N.A.	Investigative	[40]
N-methoxyquinuclidine-3-carboximidoyl chloride	DMMB3PG	Discovery agent	N.A.	Investigative	[39]
N-methoxyquinuclidine-3-carboximidoyl fluoride	DMF8IA6	Discovery agent	N.A.	Investigative	[39]
NNC 11-1314	DMSQ4TL	Discovery agent	N.A.	Investigative	[55]
NNC 11-1585	DMMX19B	Discovery agent	N.A.	Investigative	[55]
NNC 11-1607	DMZJSWI	Discovery agent	N.A.	Investigative	[55]
NOCARDIMICIN A	DMN7GO8	Discovery agent	N.A.	Investigative	[46]
Nocardimicin C	DM4SRL7	Discovery agent	N.A.	Investigative	[46]
Nocardimicin D	DM1SABZ	Discovery agent	N.A.	Investigative	[46]
Nocardimicin F	DMK02YC	Discovery agent	N.A.	Investigative	[46]
Noccardimicin E	DMXOF4Z	Discovery agent	N.A.	Investigative	[46]
Olterodine	DMTY63G	Discovery agent	N.A.	Investigative	[56]
Oxybutynine	DMJPBAX	Discovery agent	N.A.	Investigative	[57]
p-F-HHSiD	DM9CV6S	Discovery agent	N.A.	Investigative	[58]
pentylthio-TZTP	DMD8NHB	Discovery agent	N.A.	Investigative	[37]
Propionic acid 8-aza-bicyclo[3.2.1]oct-6-yl ester	DMO325J	Discovery agent	N.A.	Investigative	[38]
PTAC	DMEJ6SK	Discovery agent	N.A.	Investigative	[56]
silahexocyclium	DM4VDMP	Discovery agent	N.A.	Investigative	[49]
SULFOARECOLINE	DM8KYUE	Discovery agent	N.A.	Investigative	[59]
thiochrome	DML4TQ5	Discovery agent	N.A.	Investigative	[60]
tripitramine	DMWZ5FB	Discovery agent	N.A.	Investigative	[61]
UCB-101333-3	DMHYORU	Discovery agent	N.A.	Investigative	[62]
UH-AH 37	DMT5UMG	Discovery agent	N.A.	Investigative	[63]
vinburnine	DMO4GBK	Discovery agent	N.A.	Investigative	[37]
VU0255035	DMRKE6W	Discovery agent	N.A.	Investigative	[64]
WIN 51,708	DMY5LOB	Discovery agent	N.A.	Investigative	[65]
WIN 62,577	DMGOQY2	Discovery agent	N.A.	Investigative	[65]
[3H]oxotremorine-M	DM5L7D3	Discovery agent	N.A.	Investigative	[37]
[3H]QNB	DMC1WHR	Discovery agent	N.A.	Investigative	[66]

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
Sjogren's syndrome	4A43.2	Salivary gland tissue	3.56E-01	-0.25	-0.73
Chronic obstructive pulmonary disease	CA23	Lung tissue	2.09E-01	-0.04	-0.11
Chronic obstructive pulmonary disease	CA23	Small airway epithelium	1.52E-02	-0.06	-0.39
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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