Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTZ9SOR)

• DTT Name: Muscarinic acetylcholine receptor M1 (CHRM1)
• Synonyms: M1 receptor
• Gene Name: CHRM1
• DTT Type: Successful target; [1]
• Related Disease:
  Abdominal pelvic pain [ICD-11: MD81]
  Chronic obstructive pulmonary disease [ICD-11: CA22]
  Corneal disease [ICD-11: 9A76-9A78]
  Dystonic disorder [ICD-11: 8A02]
  Functional bladder disorder [ICD-11: GC50]
  Gastric ulcer [ICD-11: DA60]
  Glaucoma [ICD-11: 9C61]
  Hyperhidrosis [ICD-11: EE00]
  Irritable bowel syndrome [ICD-11: DD91]
  Parkinsonism [ICD-11: 8A00]
  Peptic ulcer [ICD-11: DA61]
  Sebaceous gland disorder [ICD-11: ED91]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: ACM1_HUMAN
• TTD ID: T28893
• Sequence:
  MNTSAPPAVSPNITVLAPGKGPWQVAFIGITTGLLSLATVTGNLLVLISFKVNTELKTVN
  NYFLLSLACADLIIGTFSMNLYTTYLLMGHWALGTLACDLWLALDYVASNASVMNLLLIS
  FDRYFSVTRPLSYRAKRTPRRAALMIGLAWLVSFVLWAPAILFWQYLVGERTVLAGQCYI
  QFLSQPIITFGTAMAAFYLPVTVMCTLYWRIYRETENRARELAALQGSETPGKGGGSSSS
  SERSQPGAEGSPETPPGRCCRCCRAPRLLQAYSWKEEEEEDEGSMESLTSSEGEEPGSEV
  VIKMPMVDPEAQAPTKQPPRSSPNTVKRPTKKGRDRAGKGQKPRGKEQLAKRKTFSLVKE
  KKAARTLSAILLAFILTWTPYNIMVLVSTFCKDCVPETLWELGYWLCYVNSTINPMCYAL
  CNKAFRDTFRLLLLCRWDKRRWRKIPKRPGSVHRTPSRQC
• Function: Primary transducing effect is Pi turnover. 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.
• 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 (q) signalling events (R-HSA-416476)
  Muscarinic acetylcholine receptors (R-HSA-390648)

Molecular Interaction Atlas (MIA) of This DTT

15 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ACECLIDINE	DMOLNCZ	Glaucoma/ocular hypertension	9C61	Approved	[2]
Benztropine	DMGZOVN	Parkinson disease	8A00.0	Approved	[3], [4]
Biperiden	DME78OA	Parkinson disease	8A00.0	Approved	[5]
Clidinium	DMUMQZ0	Abdominal stomach pain	DD91.4	Approved	[6]
Cycrimine	DM8C43Q	Parkinson disease	8A00.0	Approved	[7]
Dicyclomine	DMZSDGX	Functional bowel syndrome	DD91.0	Approved	[8], [9]
Diphemanil Methylsulfate	DMXVU6D	Peptic ulcer	DA61	Approved	[10]
Fesoterodine fumarate	DM13495	Overactive bladder	GC50.0	Approved	[11]
Glycopyrrolate	DM2M3ZA	Anaesthesia	9A78.6	Approved	[12], [13]
Metixene	DM0JE6N	Parkinson disease	8A00.0	Approved	[14]
Oxyphenonium	DMMQHOZ	Visceral spasms	MD81.4	Approved	[15]
Pirenzepine	DMP6M1N	Peptic ulcer	DA61	Approved	[1], [16]
Propantheline	DM2EN6G	Excessive sweating	EE00.Z	Approved	[17]
SMT-D002	DM1I93C	Seborrhea	ED91.2	Approved	[18]
Trihexyphenidyl	DMB19L8	Dystonia	8A02	Approved	[19]

17 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Darotropium + 642444	DMR2JD4	Chronic obstructive pulmonary disease	CA22	Phase 3	[20]
Nebracetam	DMFD249	Parkinson disease	8A00.0	Phase 3	[21]
(S)-oxybutynin	DMAV426	Urinary incontinence	MF50.2	Phase 2	[22]
FP-1097	DMC1F2T	Urinary incontinence	MF50.2	Phase 2	[23]
N-DESMETHYLCLOZAPINE	DMVIRN3	Schizoaffective disorder	6A21	Phase 2	[24]
NGX-267	DMJKBAY	Schizophrenia	6A20	Phase 2	[25]
SR-46559A	DMW6UA3	Cognitive impairment	6D71	Phase 2	[11]
Xanomeline tartrate	DMXG5WU	Parkinson disease	8A00.0	Phase 2	[25], [26]
AC-262271	DM36WTQ	Glaucoma/ocular hypertension	9C61	Phase 1	[27]
ANAVEX 2-73	DM67OU4	Alzheimer disease	8A20	Phase 1	[28], [29]
Arecoline	DMFJZK3	Parkinson disease	8A00.0	Phase 1	[30]
AZD-6088	DM0WCR4	Neuropathic pain	8E43.0	Phase 1	[31]
B7-2/GM-CSF	DM0LKHV	Dementia	6D80-6D86	Phase 1	[20]
MCD-386	DMFIS4D	Alzheimer disease	8A20	Phase 1	[32]
TAK-071	DMKUT08	Alzheimer disease	8A20	Phase 1	[28], [29]
Thiopilocarpine	DMOLFAU	Cognitive impairment	6D71	Phase 1	[33]
WST-057	DM9PNR6	Peripheral neuropathy	8C0Z	Phase 1	[28]

15 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Telenzepine	DM6PVWS	Chronic obstructive pulmonary disease	CA22	Discontinued in Preregistration	[34]
Darotropium	DMJ4WR6	Chronic obstructive pulmonary disease	CA22	Discontinued in Phase 2	[20]
Declopramide	DM5QFT4	Inflammatory bowel disease	DD72	Discontinued in Phase 2	[35]
Rispenzepine	DMVHT6F	Chronic obstructive pulmonary disease	CA22	Discontinued in Phase 2	[36]
Talsaclidine fumarate	DM2KH9Y	Alzheimer disease	8A20	Discontinued in Phase 2	[25], [37]
YM-796	DMDXP3C	Cognitive impairment	6D71	Discontinued in Phase 2	[38]
PD-151832	DMO34NQ	Parkinson disease	8A00.0	Discontinued in Phase 1/2	[11]
ITAMELINE	DM8139E	Cognitive impairment	6D71	Discontinued in Phase 1	[11]
Sabcomeline	DMCEOAJ	N. A.	N. A.	Discontinued in Phase 1	[25]
SDZ-210-086	DM8BIV4	Cognitive impairment	6D71	Discontinued in Phase 1	[39]
TAZOMELINE	DM5PZ60	Cognitive impairment	6D71	Discontinued in Phase 1	[11]
AC-260584	DMA93D8	Schizophrenia	6A20	Terminated	[25]
Alvameline	DMLN0Y5	Alzheimer disease	8A20	Terminated	[40]
HIMBACINE	DMGAKD8	N. A.	N. A.	Terminated	[41]
WAY-132983	DM2XTB9	N. A.	N. A.	Terminated	[25], [37]

44 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	[42]
1,1-diphenyl-2-(3-tropanyl)ethanol	DMZDUSA	Discovery agent	N.A.	Investigative	[43]
1-Methyl-1-(4-pyrrolidin-1-yl-but-2-ynyl)-urea	DM9KCXI	Discovery agent	N.A.	Investigative	[44]
2,8-Dimethyl-1-oxa-8-aza-spiro[4.5]decan-3-one	DMAKZ43	Discovery agent	N.A.	Investigative	[45]
2-(4-Diethylamino-but-2-ynyl)-isoindole-1,3-dione	DM823CD	Discovery agent	N.A.	Investigative	[46]
2-Methyl-6-pyrrolidin-1-yl-hex-4-ynal oxime	DM8EV4A	Discovery agent	N.A.	Investigative	[47]
3-(3-benzylamino)-piperidin-2-one	DMYN6Z9	Discovery agent	N.A.	Investigative	[48]
3-Methyl-7-pyrrolidin-1-yl-hept-5-yn-2-one	DME81U3	Discovery agent	N.A.	Investigative	[47]
3-Tetrazol-2-yl-1-aza-bicyclo[2.2.2]octane	DMIH6JU	Discovery agent	N.A.	Investigative	[49]
3alpha-(bis-chloro-phenylmethoxy)tropane	DMBUZWQ	Discovery agent	N.A.	Investigative	[50]
4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one	DMM9X0G	Discovery agent	N.A.	Investigative	[25], [51]
6-Dimethylamino-2-methyl-hex-4-ynal oxime	DML2AC1	Discovery agent	N.A.	Investigative	[47]
7-Dimethylamino-3-methyl-hept-5-yn-2-one	DMDY2PQ	Discovery agent	N.A.	Investigative	[47]
7-Dimethylamino-hept-5-yn-2-one	DMH782V	Discovery agent	N.A.	Investigative	[47]
7-Pyrrolidin-1-yl-hept-5-yn-2-one	DMQJ26K	Discovery agent	N.A.	Investigative	[47]
A-987306	DMU34BK	Discovery agent	N.A.	Investigative	[52]
Acetic acid 8-aza-bicyclo[3.2.1]oct-6-yl ester	DMVEH40	Discovery agent	N.A.	Investigative	[53]
AF150(S)	DMOYADT	Discovery agent	N.A.	Investigative	[54], [55]
AMINOBENZTROPINE	DMT13EW	Discovery agent	N.A.	Investigative	[56]
Benzoic acid 8-aza-bicyclo[3.2.1]oct-6-yl ester	DM6T8YM	Discovery agent	N.A.	Investigative	[57]
Bo(15)PZ	DMCUJH5	Discovery agent	N.A.	Investigative	[58]
BQCA	DMSGIXK	Neurological disorder	6B60	Investigative	[59]
BRL-55473	DMEMZ6Q	Discovery agent	N.A.	Investigative	[60]
CARAMIPEN	DMJFPA9	Discovery agent	N.A.	Investigative	[61]
Cremastrine	DMLJOGK	Discovery agent	N.A.	Investigative	[62]
DAU-5750	DMT14A7	Discovery agent	N.A.	Investigative	[63]
DAU-5884	DMEZVGK	Discovery agent	N.A.	Investigative	[64]
DAU-6202	DMM5SI1	Discovery agent	N.A.	Investigative	[65]
Difluorobenztropine	DM8ABD6	Discovery agent	N.A.	Investigative	[50]
FLUMEZAPINE	DMW0HOG	Discovery agent	N.A.	Investigative	[66]
FM1-10	DM5782Z	Discovery agent	N.A.	Investigative	[67]
FM1-43	DMAP8VY	Discovery agent	N.A.	Investigative	[67]
GNF-PF-5618	DMT8VUS	Discovery agent	N.A.	Investigative	[68]
hexocyclium	DM0HS7L	Discovery agent	N.A.	Investigative	[69]
ISOCLOZAPINE	DM52CPU	Discovery agent	N.A.	Investigative	[70]
ISOLOXAPINE	DMH1BN4	Discovery agent	N.A.	Investigative	[71]
LY-593039	DMQVF41	Discovery agent	N.A.	Investigative	[25]
N-(4-Dimethylamino-but-2-ynyl)-N-methyl-acetamide	DMB3E7H	Discovery agent	N.A.	Investigative	[47]
N-methoxyquinuclidine-3-carboximidoyl chloride	DMMB3PG	Discovery agent	N.A.	Investigative	[60]
N-methoxyquinuclidine-3-carboximidoyl fluoride	DMF8IA6	Discovery agent	N.A.	Investigative	[60]
Propionic acid 8-aza-bicyclo[3.2.1]oct-6-yl ester	DMO325J	Discovery agent	N.A.	Investigative	[57]
R-dimethindene	DM6FVZW	Discovery agent	N.A.	Investigative	[72]
RR(17)PZ	DMP9RLE	Discovery agent	N.A.	Investigative	[58]
SULFOARECOLINE	DM8KYUE	Discovery agent	N.A.	Investigative	[73]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
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
Parkinson's disease	8A00.0	Substantia nigra tissue	5.59E-01	0.19	0.41
Alzheimer's disease	8A00.0	Entorhinal cortex	4.61E-07	-0.59	-0.73
Irritable bowel syndrome	DD91.0	Rectal colon tissue	1.26E-01	-0.03	-0.16
Type 2 diabetes	5A11	Liver tissue	5.87E-01	0.07	1.02

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