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]
BioChemical Class
GPCR rhodopsin
UniProt ID
ACM1_HUMAN
TTD ID
T28893
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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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

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas 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]
Biperiden DME78OA Parkinson disease 8A00.0 Approved [4]
Clidinium DMUMQZ0 Abdominal stomach pain DD91.4 Approved [5]
Cycrimine DM8C43Q Parkinson disease 8A00.0 Approved [6]
Dicyclomine DMZSDGX Functional bowel syndrome DD91.0 Approved [7]
Diphemanil Methylsulfate DMXVU6D Peptic ulcer DA61 Approved [8]
Fesoterodine fumarate DM13495 Overactive bladder GC50.0 Approved [9]
Glycopyrrolate DM2M3ZA Anaesthesia 9A78.6 Approved [10]
Metixene DM0JE6N Parkinson disease 8A00.0 Approved [11]
Oxyphenonium DMMQHOZ Visceral spasms MD81.4 Approved [12]
Pirenzepine DMP6M1N Peptic ulcer DA61 Approved [1]
Propantheline DM2EN6G Excessive sweating EE00.Z Approved [13]
SMT-D002 DM1I93C Seborrhea ED91.2 Approved [14]
Trihexyphenidyl DMB19L8 Dystonia 8A02 Approved [15]
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⏷ Show the Full List of 15 Approved Drug(s)
17 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Nebracetam DMFD249 Parkinson disease 8A00.0 Phase 3 [16]
(S)-oxybutynin DMAV426 Urinary incontinence MF50.2 Phase 2 [17]
FP-1097 DMC1F2T Urinary incontinence MF50.2 Phase 2 [18]
N-DESMETHYLCLOZAPINE DMVIRN3 Schizoaffective disorder 6A21 Phase 2 [19]
NGX-267 DMJKBAY Schizophrenia 6A20 Phase 2 [20]
SR-46559A DMW6UA3 Cognitive impairment 6D71 Phase 2 [9]
Xanomeline tartrate DMXG5WU Parkinson disease 8A00.0 Phase 2 [20]
AC-262271 DM36WTQ Glaucoma/ocular hypertension 9C61 Phase 1 [21]
ANAVEX 2-73 DM67OU4 Alzheimer disease 8A20 Phase 1 [22]
ANAVEX 3-71 DM31634 Frontotemporal dementia 6D83 Phase 1 [23]
Arecoline DMFJZK3 Parkinson disease 8A00.0 Phase 1 [24]
AZD-6088 DM0WCR4 Neuropathic pain 8E43.0 Phase 1 [25]
B7-2/GM-CSF DM0LKHV Dementia 6D80-6D86 Phase 1 [26]
MCD-386 DMFIS4D Alzheimer disease 8A20 Phase 1 [27]
TAK-071 DMKUT08 Alzheimer disease 8A20 Phase 1 [22]
Thiopilocarpine DMOLFAU Cognitive impairment 6D71 Phase 1 [28]
WST-057 DM9PNR6 Peripheral neuropathy 8C0Z Phase 1 [22]
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⏷ Show the Full List of 17 Clinical Trial Drug(s)
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 [29]
Darotropium DMJ4WR6 Chronic obstructive pulmonary disease CA22 Discontinued in Phase 2 [26]
Declopramide DM5QFT4 Inflammatory bowel disease DD72 Discontinued in Phase 2 [30]
Rispenzepine DMVHT6F Chronic obstructive pulmonary disease CA22 Discontinued in Phase 2 [31]
Talsaclidine fumarate DM2KH9Y Alzheimer disease 8A20 Discontinued in Phase 2 [20]
YM-796 DMDXP3C Cognitive impairment 6D71 Discontinued in Phase 2 [32]
PD-151832 DMO34NQ Parkinson disease 8A00.0 Discontinued in Phase 1/2 [9]
ITAMELINE DM8139E Cognitive impairment 6D71 Discontinued in Phase 1 [9]
Sabcomeline DMCEOAJ N. A. N. A. Discontinued in Phase 1 [20]
SDZ-210-086 DM8BIV4 Cognitive impairment 6D71 Discontinued in Phase 1 [33]
TAZOMELINE DM5PZ60 Cognitive impairment 6D71 Discontinued in Phase 1 [9]
AC-260584 DMA93D8 Schizophrenia 6A20 Terminated [20]
Alvameline DMLN0Y5 Alzheimer disease 8A20 Terminated [34]
HIMBACINE DMGAKD8 N. A. N. A. Terminated [35]
WAY-132983 DM2XTB9 N. A. N. A. Terminated [20]
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⏷ Show the Full List of 15 Discontinued Drug(s)
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 [36]
1,1-diphenyl-2-(3-tropanyl)ethanol DMZDUSA Discovery agent N.A. Investigative [37]
1-Methyl-1-(4-pyrrolidin-1-yl-but-2-ynyl)-urea DM9KCXI Discovery agent N.A. Investigative [38]
2,8-Dimethyl-1-oxa-8-aza-spiro[4.5]decan-3-one DMAKZ43 Discovery agent N.A. Investigative [39]
2-(4-Diethylamino-but-2-ynyl)-isoindole-1,3-dione DM823CD 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]
3alpha-(bis-chloro-phenylmethoxy)tropane DMBUZWQ Discovery agent N.A. Investigative [44]
4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one DMM9X0G Discovery agent N.A. Investigative [20]
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-987306 DMU34BK 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]
AF150(S) DMOYADT Discovery agent N.A. Investigative [47]
AMINOBENZTROPINE DMT13EW Discovery agent N.A. Investigative [48]
Benzoic acid 8-aza-bicyclo[3.2.1]oct-6-yl ester DM6T8YM Discovery agent N.A. Investigative [49]
Bo(15)PZ DMCUJH5 Discovery agent N.A. Investigative [50]
BQCA DMSGIXK Neurological disorder 6B60 Investigative [51]
BRL-55473 DMEMZ6Q Discovery agent N.A. Investigative [52]
CARAMIPEN DMJFPA9 Discovery agent N.A. Investigative [53]
Cremastrine DMLJOGK Discovery agent N.A. Investigative [54]
DAU-5750 DMT14A7 Discovery agent N.A. Investigative [55]
DAU-5884 DMEZVGK Discovery agent N.A. Investigative [56]
DAU-6202 DMM5SI1 Discovery agent N.A. Investigative [57]
Difluorobenztropine DM8ABD6 Discovery agent N.A. Investigative [44]
FLUMEZAPINE DMW0HOG Discovery agent N.A. Investigative [58]
FM1-10 DM5782Z Discovery agent N.A. Investigative [59]
FM1-43 DMAP8VY Discovery agent N.A. Investigative [59]
GNF-PF-5618 DMT8VUS Discovery agent N.A. Investigative [60]
hexocyclium DM0HS7L Discovery agent N.A. Investigative [61]
ISOCLOZAPINE DM52CPU Discovery agent N.A. Investigative [62]
ISOLOXAPINE DMH1BN4 Discovery agent N.A. Investigative [63]
LY-593039 DMQVF41 Discovery agent N.A. Investigative [20]
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 [52]
N-methoxyquinuclidine-3-carboximidoyl fluoride DMF8IA6 Discovery agent N.A. Investigative [52]
Propionic acid 8-aza-bicyclo[3.2.1]oct-6-yl ester DMO325J Discovery agent N.A. Investigative [49]
R-dimethindene DM6FVZW Discovery agent N.A. Investigative [64]
RR(17)PZ DMP9RLE Discovery agent N.A. Investigative [50]
SULFOARECOLINE DM8KYUE Discovery agent N.A. Investigative [65]
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⏷ Show the Full List of 44 Investigative Drug(s)

Molecular Expression Atlas (MEA) of This DTT

Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas 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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⏷ Show the Full List of DTT Expression Under 8 Diseases

References

1 Negative crosstalk between M1 and M2 muscarinic autoreceptors involves endogenous adenosine activating A1 receptors at the rat motor endplate. Neurosci Lett. 2009 Aug 14;459(3):127-31.
2 Design, synthesis, and neurochemical evaluation of 5-(3-alkyl-1,2,4- oxadiazol-5-yl)-1,4,5,6-tetrahydropyrimidines as M1 muscarinic receptor agonists. J Med Chem. 1993 Apr 2;36(7):842-7.
3 Formulation and biopharmaceutical evaluation of transdermal patch containing benztropine. Int J Pharm. 2008 Jun 5;357(1-2):55-60.
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30 Pharmacokinetics and central nervous system toxicity of declopramide (3-chloroprocainamide) in rats and mice. Anticancer Drugs. 1999 Jan;10(1):79-88.
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32 YM796, a novel muscarinic agonist, improves the impairment of learning behavior in a rat model of chronic focal cerebral ischemia. Brain Res. 1995 Jan 9;669(1):107-14.
33 Influence of the cholinergic agonist SDZ 210-086 on sleep in healthy subjects. Neuropsychopharmacology. 1993 Nov;9(3):225-32.
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36 Synthesis and biological evaluation of [125I]- and [123I]-4-iododexetimide, a potent muscarinic cholinergic receptor antagonist. J Med Chem. 1989 May;32(5):1057-62.
37 Discovery of (3-endo)-3-(2-cyano-2,2-diphenylethyl)-8,8-dimethyl-8-azoniabicyclo[3.2.1]octane bromide as an efficacious inhaled muscarinic acetylch... Bioorg Med Chem Lett. 2009 Aug 15;19(16):4560-2.
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39 Synthesis and modeling studies of a potent conformationally rigid muscarinic agonist: 1-azabicyclo[2.2.1]heptanespirofuranone. J Med Chem. 1998 Oct 22;41(22):4181-5.
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42 Designing active template molecules by combining computational de novo design and human chemist's expertise. J Med Chem. 2007 Apr 19;50(8):1925-32.
43 Synthesis and muscarinic activities of quinuclidin-3-yltriazole and -tetrazole derivatives. J Med Chem. 1992 Apr 3;35(7):1280-90.
44 Structure-activity relationship studies on a novel series of (S)-2beta-substituted 3alpha-[bis(4-fluoro- or 4-chlorophenyl)methoxy]tropane analogue... J Med Chem. 2006 Oct 19;49(21):6391-9.
45 cis-4-(Piperazin-1-yl)-5,6,7a,8,9,10,11,11a-octahydrobenzofuro[2,3-h]quinazolin-2-amine (A-987306), a new histamine H4R antagonist that blocks pain... J Med Chem. 2008 Nov 27;51(22):7094-8.
46 6beta-Acetoxynortropane: a potent muscarinic agonist with apparent selectivity toward M2-receptors. J Med Chem. 1998 Jun 4;41(12):2047-55.
47 M1 muscarinic agonists target major hallmarks of Alzheimer's disease--an update. Curr Alzheimer Res. 2007 Dec;4(5):577-80.
48 3'-Chloro-3 alpha-(diphenylmethoxy)tropane but not 4'-chloro-3 alpha-(diphenylmethoxy)tropane produces a cocaine-like behavioral profile. J Med Chem. 1997 Mar 14;40(6):851-7.
49 6beta-Acyloxy(nor)tropanes: affinities for antagonist/agonist binding sites on transfected and native muscarinic receptors. J Med Chem. 2000 Jun 29;43(13):2514-22.
50 On the use of nonfluorescent dye labeled ligands in FRET-based receptor binding studies. J Med Chem. 2005 Dec 1;48(24):7847-59.
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54 Cremastrine, a pyrrolizidine alkaloid from Cremastra appendiculata. J Nat Prod. 2005 Apr;68(4):572-3.
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56 Doi: 10.1038/bjp.2008.208
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58 Synthesis and pharmacological evaluation of a series of 4-piperazinylpyrazolo[3,4-b]- and -[4,3-b][1,5]benzodiazepines as potential anxiolytics. J Med Chem. 1989 Dec;32(12):2573-82.
59 Design and synthesis of a fluorescent muscarinic antagonist. Bioorg Med Chem Lett. 2008 Jan 15;18(2):825-7.
60 Nocardimicins A, B, C, D, E, and F, siderophores with muscarinic M3 receptor inhibiting activity from Nocardia sp. TP-A0674. J Nat Prod. 2005 Jul;68(7):1061-5.
61 Hexocyclium derivatives with a high selectivity for smooth muscle muscarinic receptors. Br J Pharmacol. 1990 May;100(1):150-2.
62 Chloro-substituted, sterically hindered 5,11-dicarbo analogues of clozapine as potential chiral antipsychotic agents. J Med Chem. 1990 Feb;33(2):809-14.
63 Synthesis of clozapine analogues and their affinity for clozapine and spiroperidol binding sites in rat brain. J Med Chem. 1981 Sep;24(9):1021-6.
64 Characterization of novel selective H1-antihistamines for clinical evaluation in the treatment of insomnia. J Med Chem. 2009 Sep 10;52(17):5307-10.
65 Heterocyclic muscarinic agonists. Synthesis and biological activity of some bicyclic sulfonium arecoline bioisosteres. J Med Chem. 1988 Jul;31(7):1312-6.