Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTH18TF)

• DTT Name: Muscarinic acetylcholine receptor M5 (CHRM5)
• Synonyms: CHRM5
• Gene Name: CHRM5
• DTT Type: Successful target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: ACM5_HUMAN
• TTD ID: T79961
• Sequence:
  MEGDSYHNATTVNGTPVNHQPLERHRLWEVITIAAVTAVVSLITIVGNVLVMISFKVNSQ
  LKTVNNYYLLSLACADLIIGIFSMNLYTTYILMGRWALGSLACDLWLALDYVASNASVMN
  LLVISFDRYFSITRPLTYRAKRTPKRAGIMIGLAWLISFILWAPAILCWQYLVGKRTVPL
  DECQIQFLSEPTITFGTAIAAFYIPVSVMTILYCRIYRETEKRTKDLADLQGSDSVTKAE
  KRKPAHRALFRSCLRCPRPTLAQRERNQASWSSSRRSTSTTGKPSQATGPSANWAKAEQL
  TTCSSYPSSEDEDKPATDPVLQVVYKSQGKESPGEEFSAEETEETFVKAETEKSDYDTPN
  YLLSPAAAHRPKSQKCVAYKFRLVVKADGNQETNNGCHKVKIMPCPFPVAKEPSTKGLNP
  NPSHQMTKRKRVVLVKERKAAQTLSAILLAFIITWTPYNIMVLVSTFCDKCVPVTLWHLG
  YWLCYVNSTVNPICYALCNRTFRKTFKMLLLCRWKKKKVEEKLYWQGNSKLP
• 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:
  Calcium signaling pathway (hsa04020)
  Neuroactive ligand-receptor interaction (hsa04080)
  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

31 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ACECLIDINE	DMOLNCZ	Glaucoma/ocular hypertension	9C61	Approved	[2]
Anisodine	DMNOSWU	Central and peripheral nervous disease	8A04-8E7Z	Approved	[3]
Anisotropine Methylbromide	DMIJRF0	Gastric ulcer	DA60	Approved	[4]
Atropine	DMEN6X7	Organophosphate poisoning	NE6Z	Approved	[5]
Belladonna	DM2RBWK	Colitis	1A40.Z	Approved	[6]
Bethanechol	DMCLHO0	Urinary retention	MF50.3	Approved	[7]
Butylscopolamine	DMZKXB7	Dysmenorrhea	GA34.3	Approved	[8]
Choline alfoscerate	DMOI1ZF	Amnesia	MB21.1	Approved	[9]
Cimetropium bromide	DMZHPNE	Gastric motility disorder	DA21	Approved	[10]
Cryptenamine Acetates	DMHCTAL	Hypertension	BA00-BA04	Approved	[11]
Cyclopentolate	DMA8LM5	Examination of eyes or vision	QA00.6	Approved	[12]
Emepronium	DMCOAVT	Urinary incontinence	MF50.2	Approved	[13]
Flavoxate	DMKV4NL	Dysuria	MF50.7	Approved	[14]
Flutropium bromide	DMU54C3	Cough	MD12	Approved	[10]
Homatropine Methylbromide	DMGBPSH	Cough	MD12	Approved	[15]
Hyoscyamine	DM804UR	Dysuria	MF50.7	Approved	[16]
Ispaghula	DMWCRN1	Irritable bowel syndrome	DD91.0	Approved	[17]
Mebeverine	DMNOBFQ	Irritable bowel syndrome	DD91.0	Approved	[17]
Mepenzolate	DM8YU2F	Gastric ulcer	DA60	Approved	[18]
Methantheline	DM8X4A1	Gastric ulcer	DA60	Approved	[19]
Oxitropium bromide	DM9FKSR	Asthma	CA23	Approved	[10]
Oxyphencyclimine	DM3TABW	Peptic ulcer	DA61	Approved	[20]
Pilocarpine	DMV9ADG	Glaucoma/ocular hypertension	9C61	Approved	[21]
Pramiracetam	DM2FHG3	Brain disease	8C70-8E61	Approved (orphan drug)	[1]
Prifinium	DMMZB0K	Irritable bowel syndrome	DD91.0	Approved	[22]
Procyclidine	DMHFJDT	Parkinson disease	8A00.0	Approved	[23]
Promazine	DMZAL7W	Acute intermittent hepatic porphyria	5C58.11	Approved	[24]
Propiverine	DMUWBIJ	Urinary incontinence	MF50.2	Approved	[25]
Tridihexethyl	DMVLHNI	Acquired nystagmus	9C84	Approved	[26]
Trospium	DMX6RTG	Overactive bladder	GC50.0	Approved	[15]
Umeclidinium	DM4E8O9	Chronic obstructive pulmonary disease	CA22	Approved	[27]

4 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
L-651582	DMWTPCA	Solid tumour/cancer	2A00-2F9Z	Phase 3	[28]
OrM3	DMEARCM	Chronic obstructive pulmonary disease	CA22	Phase 2b	[29]
GSK233705	DMXUCG3	Chronic obstructive pulmonary disease	CA22	Phase 2	[29]
Dexpirronium	DMAE9I0	Chronic obstructive pulmonary disease	CA22	Phase 1	[9]

7 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Benactyzine	DM0J92L	Depression	6A70-6A7Z	Withdrawn from market	[30]
BMS-181168	DMGPHTJ	Cognitive impairment	6D71	Discontinued in Phase 2	[31]
DDP-200	DMMV6RK	Urinary incontinence	MF50.2	Discontinued in Phase 2	[32]
FK-584	DMR2FPO	Central and peripheral nervous disease	8A04-8E7Z	Discontinued in Phase 2	[33]
AM-831	DMO7920	Schizophrenia	6A20	Discontinued in Phase 1	[34]
RS 86	DMKQV9A	Alzheimer disease	8A20	Terminated	[36]
SU-740	DMWCR1Z	Stomach ulcer	DA60.Z	Terminated	[37]

1 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Org-23366	DMHQUM2	Schizophrenia	6A20	Preclinical	[35]

42 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	[38]
1-Methyl-1-(4-pyrrolidin-1-yl-but-2-ynyl)-urea	DM9KCXI	Discovery agent	N.A.	Investigative	[39]
2,8-Dimethyl-1-oxa-8-aza-spiro[4.5]decan-3-one	DMAKZ43	Discovery agent	N.A.	Investigative	[40]
2-Methyl-6-pyrrolidin-1-yl-hex-4-ynal oxime	DM8EV4A	Discovery agent	N.A.	Investigative	[41]
3-(3-benzylamino)-piperidin-2-one	DMYN6Z9	Discovery agent	N.A.	Investigative	[42]
3-Methyl-7-pyrrolidin-1-yl-hept-5-yn-2-one	DME81U3	Discovery agent	N.A.	Investigative	[41]
3-Tetrazol-2-yl-1-aza-bicyclo[2.2.2]octane	DMIH6JU	Discovery agent	N.A.	Investigative	[43]
4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one	DMM9X0G	Discovery agent	N.A.	Investigative	[44]
6-Dimethylamino-2-methyl-hex-4-ynal oxime	DML2AC1	Discovery agent	N.A.	Investigative	[41]
7-Dimethylamino-3-methyl-hept-5-yn-2-one	DMDY2PQ	Discovery agent	N.A.	Investigative	[41]
7-Dimethylamino-hept-5-yn-2-one	DMH782V	Discovery agent	N.A.	Investigative	[41]
7-Pyrrolidin-1-yl-hept-5-yn-2-one	DMQJ26K	Discovery agent	N.A.	Investigative	[41]
A-867744	DM96F8U	Discovery agent	N.A.	Investigative	[45]
Acetic acid 8-aza-bicyclo[3.2.1]oct-6-yl ester	DMVEH40	Discovery agent	N.A.	Investigative	[46]
alpha-conotoxin AuIB	DM96EJ1	Discovery agent	N.A.	Investigative	[9]
alpha-conotoxin GI	DMHO634	Discovery agent	N.A.	Investigative	[9]
alpha-conotoxin PnIA	DM1QOY0	Discovery agent	N.A.	Investigative	[9]
Aprophen	DM0VBUL	Discovery agent	N.A.	Investigative	[30]
Benzoic acid 8-aza-bicyclo[3.2.1]oct-6-yl ester	DM6T8YM	Discovery agent	N.A.	Investigative	[46]
BHT-3034	DMZRS7A	Myasthenia gravis	8C6Y	Investigative	[9]
BRL-55473	DMEMZ6Q	Discovery agent	N.A.	Investigative	[47]
Cremastrine	DMLJOGK	Discovery agent	N.A.	Investigative	[48]
CRTX-070	DMBV79R	Allergic rhinitis	CA08.0	Investigative	[9]
FLUMEZAPINE	DMW0HOG	Discovery agent	N.A.	Investigative	[49]
FM1-10	DM5782Z	Discovery agent	N.A.	Investigative	[50]
FM1-43	DMAP8VY	Discovery agent	N.A.	Investigative	[50]
GNF-PF-5618	DMT8VUS	Discovery agent	N.A.	Investigative	[51]
ISOCLOZAPINE	DM52CPU	Discovery agent	N.A.	Investigative	[52]
ISOLOXAPINE	DMH1BN4	Discovery agent	N.A.	Investigative	[53]
JWB-1-84-1	DMXZ9RF	Neurological disorder	6B60	Investigative	[9]
Muscarine	DMNDUJ5	Discovery agent	N.A.	Investigative	[54]
N-(4-Dimethylamino-but-2-ynyl)-N-methyl-acetamide	DMB3E7H	Discovery agent	N.A.	Investigative	[41]
N-methoxyquinuclidine-3-carboximidoyl chloride	DMMB3PG	Discovery agent	N.A.	Investigative	[47]
N-methoxyquinuclidine-3-carboximidoyl fluoride	DMF8IA6	Discovery agent	N.A.	Investigative	[47]
NS1738	DM2S5ZF	Discovery agent	N.A.	Investigative	[55]
PF-3409409	DMEZA0T	Attention deficit hyperactivity disorder	6A05.Z	Investigative	[56]
Recombinant botulinum toxin	DMA6VCG	Neurological disorder	6B60	Investigative	[9]
SULFOARECOLINE	DM8KYUE	Discovery agent	N.A.	Investigative	[57]
VU0119498	DMPSI10	Discovery agent	N.A.	Investigative	[58]
VU0238429	DMOPLQI	Discovery agent	N.A.	Investigative	[58]
[125I]epibatidine	DMZWQH3	Discovery agent	N.A.	Investigative	[9]
[3H]cytisine	DMVLRHW	Discovery agent	N.A.	Investigative	[9]

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