Target Information
| Target General Information | Top | |||||
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| Target ID |
T28893
(Former ID: TTDS00002)
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| Target Name |
Muscarinic acetylcholine receptor M1 (CHRM1)
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| Synonyms |
M1 receptor
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| Gene Name |
CHRM1
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 12 Target-related Diseases | + | ||||
| 1 | Abdominal pelvic pain [ICD-11: MD81] | |||||
| 2 | Chronic obstructive pulmonary disease [ICD-11: CA22] | |||||
| 3 | Corneal disease [ICD-11: 9A76-9A78] | |||||
| 4 | Dystonic disorder [ICD-11: 8A02] | |||||
| 5 | Functional bladder disorder [ICD-11: GC50] | |||||
| 6 | Gastric ulcer [ICD-11: DA60] | |||||
| 7 | Glaucoma [ICD-11: 9C61] | |||||
| 8 | Hyperhidrosis [ICD-11: EE00] | |||||
| 9 | Irritable bowel syndrome [ICD-11: DD91] | |||||
| 10 | Parkinsonism [ICD-11: 8A00] | |||||
| 11 | Peptic ulcer [ICD-11: DA61] | |||||
| 12 | Sebaceous gland disorder [ICD-11: ED91] | |||||
| 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.
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| BioChemical Class |
GPCR rhodopsin
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| UniProt ID | ||||||
| Sequence |
MNTSAPPAVSPNITVLAPGKGPWQVAFIGITTGLLSLATVTGNLLVLISFKVNTELKTVN
NYFLLSLACADLIIGTFSMNLYTTYLLMGHWALGTLACDLWLALDYVASNASVMNLLLIS FDRYFSVTRPLSYRAKRTPRRAALMIGLAWLVSFVLWAPAILFWQYLVGERTVLAGQCYI QFLSQPIITFGTAMAAFYLPVTVMCTLYWRIYRETENRARELAALQGSETPGKGGGSSSS SERSQPGAEGSPETPPGRCCRCCRAPRLLQAYSWKEEEEEDEGSMESLTSSEGEEPGSEV VIKMPMVDPEAQAPTKQPPRSSPNTVKRPTKKGRDRAGKGQKPRGKEQLAKRKTFSLVKE KKAARTLSAILLAFILTWTPYNIMVLVSTFCKDCVPETLWELGYWLCYVNSTINPMCYAL CNKAFRDTFRLLLLCRWDKRRWRKIPKRPGSVHRTPSRQC Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| ADReCS ID | BADD_A00273 ; BADD_A02700 ; BADD_A02979 ; BADD_A04075 | |||||
| HIT2.0 ID | T93L35 | |||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Approved Drug(s) | [+] 14 Approved Drugs | + | ||||
| 1 | ACECLIDINE | Drug Info | Approved | Glaucoma/ocular hypertension | [5], [4] | |
| 2 | Benztropine | Drug Info | Approved | Parkinson disease | [6], [7] | |
| 3 | Biperiden | Drug Info | Approved | Parkinson disease | [4] | |
| 4 | Clidinium | Drug Info | Approved | Irritable bowel syndrome | [4], [8], [9] | |
| 5 | Cycrimine | Drug Info | Approved | Parkinson disease | [10] | |
| 6 | Dicyclomine | Drug Info | Approved | Functional bowel syndrome | [4] | |
| 7 | Diphemanil Methylsulfate | Drug Info | Approved | Peptic ulcer | [11] | |
| 8 | Fesoterodine fumarate | Drug Info | Approved | Overactive bladder | [12] | |
| 9 | Glycopyrrolate | Drug Info | Approved | Anaesthesia | [13], [14] | |
| 10 | Metixene | Drug Info | Approved | Parkinson disease | [15], [16] | |
| 11 | Oxyphenonium | Drug Info | Approved | Visceral spasms | [4] | |
| 12 | Pirenzepine | Drug Info | Approved | Peptic ulcer | [17], [18] | |
| 13 | SMT-D002 | Drug Info | Approved | Seborrhea | [19] | |
| 14 | Trihexyphenidyl | Drug Info | Approved | Dystonia | [4], [20], [21] | |
| Clinical Trial Drug(s) | [+] 17 Clinical Trial Drugs | + | ||||
| 1 | Darotropium + 642444 | Drug Info | Phase 3 | Chronic obstructive pulmonary disease | [22] | |
| 2 | Nebracetam | Drug Info | Phase 3 | Parkinson disease | [23] | |
| 3 | (S)-oxybutynin | Drug Info | Phase 2 | Urinary incontinence | [24] | |
| 4 | FP-1097 | Drug Info | Phase 2 | Urinary incontinence | [25] | |
| 5 | N-DESMETHYLCLOZAPINE | Drug Info | Phase 2 | Schizoaffective disorder | [26] | |
| 6 | NGX-267 | Drug Info | Phase 2 | Schizophrenia | [27] | |
| 7 | SR-46559A | Drug Info | Phase 2 | Cognitive impairment | [28] | |
| 8 | Xanomeline tartrate | Drug Info | Phase 2 | Parkinson disease | [29] | |
| 9 | AC-262271 | Drug Info | Phase 1 | Glaucoma/ocular hypertension | [31] | |
| 10 | ANAVEX 2-73 | Drug Info | Phase 1 | Alzheimer disease | [32], [33] | |
| 11 | Arecoline | Drug Info | Phase 1 | Parkinson disease | [34], [35], [36], [37] | |
| 12 | AZD-6088 | Drug Info | Phase 1 | Neuropathic pain | [38], [39] | |
| 13 | B7-2/GM-CSF | Drug Info | Phase 1 | Dementia | [40] | |
| 14 | MCD-386 | Drug Info | Phase 1 | Alzheimer disease | [41] | |
| 15 | TAK-071 | Drug Info | Phase 1 | Alzheimer disease | [32], [33] | |
| 16 | Thiopilocarpine | Drug Info | Phase 1 | Cognitive impairment | [42] | |
| 17 | WST-057 | Drug Info | Phase 1 | Peripheral neuropathy | [32] | |
| Discontinued Drug(s) | [+] 10 Discontinued Drugs | + | ||||
| 1 | Telenzepine | Drug Info | Discontinued in Preregistration | Chronic obstructive pulmonary disease | [43] | |
| 2 | Darotropium | Drug Info | Discontinued in Phase 2 | Chronic obstructive pulmonary disease | [45] | |
| 3 | Declopramide | Drug Info | Discontinued in Phase 2 | Inflammatory bowel disease | [46] | |
| 4 | Talsaclidine fumarate | Drug Info | Discontinued in Phase 2 | Alzheimer disease | [47] | |
| 5 | YM-796 | Drug Info | Discontinued in Phase 2 | Cognitive impairment | [48], [49] | |
| 6 | PD-151832 | Drug Info | Discontinued in Phase 1/2 | Parkinson disease | [50] | |
| 7 | ITAMELINE | Drug Info | Discontinued in Phase 1 | Cognitive impairment | [51] | |
| 8 | SDZ-210-086 | Drug Info | Discontinued in Phase 1 | Cognitive impairment | [52] | |
| 9 | TAZOMELINE | Drug Info | Discontinued in Phase 1 | Cognitive impairment | [53] | |
| 10 | AC-260584 | Drug Info | Terminated | Schizophrenia | [55], [56] | |
| Mode of Action | [+] 5 Modes of Action | + | ||||
| Inhibitor | [+] 36 Inhibitor drugs | + | ||||
| 1 | ACECLIDINE | Drug Info | [57] | |||
| 2 | Arecoline | Drug Info | [81] | |||
| 3 | HIMBACINE | Drug Info | [89] | |||
| 4 | 1'-Benzyl-3-phenyl-[3,4']bipiperidinyl-2,6-dione | Drug Info | [90] | |||
| 5 | 1,1-diphenyl-2-(3-tropanyl)ethanol | Drug Info | [91] | |||
| 6 | 1-Methyl-1-(4-pyrrolidin-1-yl-but-2-ynyl)-urea | Drug Info | [92] | |||
| 7 | 2,8-Dimethyl-1-oxa-8-aza-spiro[4.5]decan-3-one | Drug Info | [93] | |||
| 8 | 2-(4-Diethylamino-but-2-ynyl)-isoindole-1,3-dione | Drug Info | [94] | |||
| 9 | 3-(3-benzylamino)-piperidin-2-one | Drug Info | [95] | |||
| 10 | 3-Methyl-7-pyrrolidin-1-yl-hept-5-yn-2-one | Drug Info | [96] | |||
| 11 | 3-Tetrazol-2-yl-1-aza-bicyclo[2.2.2]octane | Drug Info | [97] | |||
| 12 | 3alpha-(bis-chloro-phenylmethoxy)tropane | Drug Info | [98] | |||
| 13 | 4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one | Drug Info | [78], [99] | |||
| 14 | 6-Dimethylamino-2-methyl-hex-4-ynal oxime | Drug Info | [96] | |||
| 15 | 7-Dimethylamino-3-methyl-hept-5-yn-2-one | Drug Info | [96] | |||
| 16 | 7-Dimethylamino-hept-5-yn-2-one | Drug Info | [96] | |||
| 17 | 7-Pyrrolidin-1-yl-hept-5-yn-2-one | Drug Info | [96] | |||
| 18 | A-987306 | Drug Info | [100] | |||
| 19 | Acetic acid 8-aza-bicyclo[3.2.1]oct-6-yl ester | Drug Info | [101] | |||
| 20 | AMINOBENZTROPINE | Drug Info | [102] | |||
| 21 | Benzoic acid 8-aza-bicyclo[3.2.1]oct-6-yl ester | Drug Info | [103] | |||
| 22 | Bo(15)PZ | Drug Info | [104] | |||
| 23 | BRL-55473 | Drug Info | [106] | |||
| 24 | CARAMIPEN | Drug Info | [107] | |||
| 25 | FLUMEZAPINE | Drug Info | [111] | |||
| 26 | FM1-10 | Drug Info | [112] | |||
| 27 | FM1-43 | Drug Info | [112] | |||
| 28 | GNF-PF-5618 | Drug Info | [113] | |||
| 29 | ISOCLOZAPINE | Drug Info | [115] | |||
| 30 | ISOLOXAPINE | Drug Info | [116] | |||
| 31 | N-(4-Dimethylamino-but-2-ynyl)-N-methyl-acetamide | Drug Info | [96] | |||
| 32 | N-methoxyquinuclidine-3-carboximidoyl chloride | Drug Info | [106] | |||
| 33 | Propionic acid 8-aza-bicyclo[3.2.1]oct-6-yl ester | Drug Info | [103] | |||
| 34 | R-dimethindene | Drug Info | [117] | |||
| 35 | RR(17)PZ | Drug Info | [104] | |||
| 36 | SULFOARECOLINE | Drug Info | [118] | |||
| Antagonist | [+] 11 Antagonist drugs | + | ||||
| 1 | Benztropine | Drug Info | [58], [59] | |||
| 2 | Biperiden | Drug Info | [60] | |||
| 3 | Clidinium | Drug Info | [61] | |||
| 4 | Dicyclomine | Drug Info | [63], [64] | |||
| 5 | Glycopyrrolate | Drug Info | [66], [67] | |||
| 6 | Oxyphenonium | Drug Info | [69] | |||
| 7 | Pirenzepine | Drug Info | [1], [70] | |||
| 8 | Trihexyphenidyl | Drug Info | [72] | |||
| 9 | (S)-oxybutynin | Drug Info | [75] | |||
| 10 | FP-1097 | Drug Info | [76] | |||
| 11 | WST-057 | Drug Info | [32] | |||
| Binder | [+] 1 Binder drugs | + | ||||
| 1 | Cycrimine | Drug Info | [62] | |||
| Modulator | [+] 12 Modulator drugs | + | ||||
| 1 | Diphemanil Methylsulfate | Drug Info | [65] | |||
| 2 | Fesoterodine fumarate | Drug Info | [4] | |||
| 3 | Metixene | Drug Info | [68] | |||
| 4 | N-DESMETHYLCLOZAPINE | Drug Info | [77] | |||
| 5 | TAK-071 | Drug Info | [32], [33] | |||
| 6 | Telenzepine | Drug Info | [84] | |||
| 7 | Declopramide | Drug Info | [85] | |||
| 8 | YM-796 | Drug Info | [87] | |||
| 9 | DAU-5750 | Drug Info | [108] | |||
| 10 | DAU-5884 | Drug Info | [109] | |||
| 11 | DAU-6202 | Drug Info | [110] | |||
| 12 | hexocyclium | Drug Info | [114] | |||
| Agonist | [+] 23 Agonist drugs | + | ||||
| 1 | SMT-D002 | Drug Info | [71] | |||
| 2 | Darotropium + 642444 | Drug Info | [73] | |||
| 3 | Nebracetam | Drug Info | [74] | |||
| 4 | NGX-267 | Drug Info | [78] | |||
| 5 | SR-46559A | Drug Info | [4] | |||
| 6 | Xanomeline tartrate | Drug Info | [78], [79] | |||
| 7 | AC-262271 | Drug Info | [80] | |||
| 8 | ANAVEX 2-73 | Drug Info | [32], [33] | |||
| 9 | AZD-6088 | Drug Info | [82] | |||
| 10 | B7-2/GM-CSF | Drug Info | [73] | |||
| 11 | MCD-386 | Drug Info | [83] | |||
| 12 | Thiopilocarpine | Drug Info | [42] | |||
| 13 | Darotropium | Drug Info | [73] | |||
| 14 | Talsaclidine fumarate | Drug Info | [78], [86] | |||
| 15 | PD-151832 | Drug Info | [4] | |||
| 16 | ITAMELINE | Drug Info | [4] | |||
| 17 | Sabcomeline | Drug Info | [78] | |||
| 18 | SDZ-210-086 | Drug Info | [88] | |||
| 19 | TAZOMELINE | Drug Info | [4] | |||
| 20 | AC-260584 | Drug Info | [78] | |||
| 21 | WAY-132983 | Drug Info | [78], [86] | |||
| 22 | BQCA | Drug Info | [105] | |||
| 23 | LY-593039 | Drug Info | [78] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Hyoscyamine | Ligand Info | |||||
| Structure Description | Muscarinic acetylcholine receptor 1 - muscarinic toxin 7 complex | PDB:6WJC | ||||
| Method | X-ray diffraction | Resolution | 2.55 Å | Mutation | No | [119] |
| PDB Sequence |
APGKGPWQVA
26 FIGITTGLLS36 LATVTGNLLV46 LISFKVNTEL56 KTVNNYFLLS66 LACADLIIGT 76 FSMNLYTTYL86 LMGHWALGTL96 ACDLWLALDY106 VASQARVMNL116 LLISFDRYFS 126 VTRPLSYRAK136 RTPRRAALMI146 GLAWLVSFVL156 WAPAILFWQY166 LVGERTVLAG 176 QCYIQFLSQP186 IITFGTAMAA196 FYLPVTVMCT206 LYWRIYRETE216 NRNIFEMLRI 1008 DEGLRLKIYK1018 DTEGYYTIGI1028 GHLLTKSPSL1038 NAAKSELDKA1048 IGRNTNGVIT 1058 KDEAEKLFNQ1068 DVDAAVRGIL1078 RNAKLKPVYD1088 SLDAVRRAAL1098 INMVFQMGET 1108 GVAGFTNSLR1118 MLQQKRWDEA1128 AVNLAKSRWY1138 NQTPNRAKRV1148 ITTFRTGTWD 1158 AYFSLVKEKK362 AARTLSAILL372 AFILTWTPYN382 IMVLVSTFCK392 DCVPETLWEL 402 GYWLCYVNST412 INPMCYALCN422 KAFRDTFRLL432 LLCRW
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| Ligand Name: Tiotropium | Ligand Info | |||||
| Structure Description | Structure of the human M1 muscarinic acetylcholine receptor bound to antagonist Tiotropium | PDB:5CXV | ||||
| Method | X-ray diffraction | Resolution | 2.70 Å | Mutation | Yes | [120] |
| PDB Sequence |
KGPWQVAFIG
29 ITTGLLSLAT39 VTGNLLVLIS49 FKVNTELKTV59 NNYFLLSLAC69 ADLIIGTFSM 79 NLYTTYLLMG89 HWALGTLACD99 LWLALDYVAS109 QASVMNLLLI119 SFDRYFSVTR 129 PLSYRAKRTP139 RRAALMIGLA149 WLVSFVLWAP159 AILFWQYLVG169 ERTVLAGQCY 179 IQFLSQPIIT189 FGTAMAAFYL199 PVTVMCTLYW209 RIYRETENRN1001 IFEMLRIDEG 1011 LRLKIYKDTE1021 GYYTIGIGHL1031 LTKSPSLNAA1041 KSELDKAIGR1051 NTNGVITKDE 1061 AEKLFNQDVD1071 AAVRGILRNA1081 KLKPVYDSLD1091 AVRRAALINM1101 VFQMGETGVA 1111 GFTNSLRMLQ1121 QKRWDEAAVN1131 LAKSRWYNQT1141 PNRAKRVITT1151 FRTGTWDAYF 355 SLVKEKKAAR365 TLSAILLAFI375 LTWTPYNIMV385 LVSTFCKDCV395 PETLWELGYW 405 LCYVNSTINP415 MCYALCNKAF425 RDTFRLLLLC435 RWDK
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Pathway Affiliation
Biological Network Descriptors
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Calcium signaling pathway | hsa04020 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| cAMP signaling pathway | hsa04024 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Neuroactive ligand-receptor interaction | hsa04080 | Affiliated Target |
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| Class: Environmental Information Processing => Signaling molecules and interaction | Pathway Hierarchy | ||
| PI3K-Akt signaling pathway | hsa04151 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Cholinergic synapse | hsa04725 | Affiliated Target |
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| Class: Organismal Systems => Nervous system | Pathway Hierarchy | ||
| Regulation of actin cytoskeleton | hsa04810 | Affiliated Target |
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| Class: Cellular Processes => Cell motility | Pathway Hierarchy | ||
| Click to Show/Hide the Information of Affiliated Human Pathways | |||
| Degree | 1 | Degree centrality | 1.07E-04 | Betweenness centrality | 0.00E+00 |
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| Closeness centrality | 1.86E-01 | Radiality | 1.31E+01 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 5.20E+01 | Topological coefficient | 1.00E+00 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Co-Targets | Top | |||||
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| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
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| Target-regulating microRNAs | ||||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 6 KEGG Pathways | + | ||||
| 1 | Calcium signaling pathway | |||||
| 2 | cAMP signaling pathway | |||||
| 3 | Neuroactive ligand-receptor interaction | |||||
| 4 | PI3K-Akt signaling pathway | |||||
| 5 | Cholinergic synapse | |||||
| 6 | Regulation of actin cytoskeleton | |||||
| Panther Pathway | [+] 3 Panther Pathways | + | ||||
| 1 | Alzheimer disease-amyloid secretase pathway | |||||
| 2 | Heterotrimeric G-protein signaling pathway-Gq alpha and Go alpha mediated pathway | |||||
| 3 | Muscarinic acetylcholine receptor 1 and 3 signaling pathway | |||||
| Reactome | [+] 2 Reactome Pathways | + | ||||
| 1 | Muscarinic acetylcholine receptors | |||||
| 2 | G alpha (q) signalling events | |||||
| WikiPathways | [+] 8 WikiPathways | + | ||||
| 1 | Monoamine GPCRs | |||||
| 2 | Calcium Regulation in the Cardiac Cell | |||||
| 3 | Regulation of Actin Cytoskeleton | |||||
| 4 | GPCRs, Class A Rhodopsin-like | |||||
| 5 | Gastrin-CREB signalling pathway via PKC and MAPK | |||||
| 6 | Secretion of Hydrochloric Acid in Parietal Cells | |||||
| 7 | GPCR ligand binding | |||||
| 8 | GPCR downstream signaling | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 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. | |||||
| REF 2 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 329). | |||||
| REF 3 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 080927. | |||||
| REF 4 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 5 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 288). | |||||
| REF 6 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7601). | |||||
| REF 7 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 040103. | |||||
| REF 8 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 366). | |||||
| REF 9 | Drug information of Clidinium, 2008. eduDrugs. | |||||
| REF 10 | Drug information of Cycrimine, 2008. eduDrugs. | |||||
| REF 11 | Drug information of Diphemanil Methylsulfate, 2008. eduDrugs. | |||||
| REF 12 | 2008 FDA drug approvals. Nat Rev Drug Discov. 2009 Feb;8(2):93-6. | |||||
| REF 13 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7459). | |||||
| REF 14 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 040568. | |||||
| REF 15 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7232). | |||||
| REF 16 | Drug information of Metixene, 2008. eduDrugs. | |||||
| REF 17 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 328). | |||||
| REF 18 | Autonomic modulation during acute myocardial ischemia by low-dose pirenzepine in conscious dogs with a healed myocardial infarction: a comparison with beta-adrenergic blockade. J Cardiovasc Pharmacol. 2003 May;41(5):671-7. | |||||
| REF 19 | Clinical pipeline report, company report or official report of Summit. | |||||
| REF 20 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7315). | |||||
| REF 21 | Drugs used to treat Parkinson's disease, present status and future directions. CNS Neurol Disord Drug Targets. 2008 Oct;7(4):321-42. | |||||
| REF 22 | ClinicalTrials.gov (NCT01316900) 24-week Trial Comparing GSK573719/GW642444 With GW642444 and With Tiotropium in Chronic Obstructive Pulmonary Disease. U.S. National Institutes of Health. | |||||
| REF 23 | Nefiracetam ameliorates associative learning impairment in the scopolamine-injected older rabbit. Med Sci Monit. 2002 Apr;8(4):BR105-12. | |||||
| REF 24 | A phase 2, randomized, double-blind, efficacy and safety study of oxybutynin vaginal ring for alleviation of overactive bladder symptoms in women. J Urol. 2014 Apr;191(4):1014-21. | |||||
| REF 25 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800019662) | |||||
| REF 26 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 333). | |||||
| REF 27 | ClinicalTrials.gov (NCT00637793) Study of NGX267 Oral Capsules in Patients With Xerostomia Associated With Sjorgren's Syndrome. U.S. National Institutes of Health. | |||||
| REF 28 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001599) | |||||
| REF 29 | The M1/M4 preferring agonist xanomeline is analgesic in rodent models of chronic inflammatory and neuropathic pain via central site of action. Pain. 2011 Dec;152(12):2852-60. | |||||
| REF 30 | ClinicalTrials.gov (NCT04442945) A Double-blind, Randomized, Placebo-controlled, Phase 1 Safety and Tolerability, and Pharmacokinetics Study of ANAVEX3-71. U.S.National Institutes of Health. | |||||
| REF 31 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800033965) | |||||
| REF 32 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 33 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 34 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 296). | |||||
| REF 35 | M1 receptor activation is a requirement for arecoline analgesia. Farmaco. 2001 May-Jul;56(5-7):383-5. | |||||
| REF 36 | Arecoline excites rat locus coeruleus neurons by activating the M2-muscarinic receptor. Chin J Physiol. 2000 Mar 31;43(1):23-8. | |||||
| REF 37 | Arecoline excites the colonic smooth muscle motility via M3 receptor in rabbits. Chin J Physiol. 2004 Jun 30;47(2):89-94. | |||||
| REF 38 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7822). | |||||
| REF 39 | ClinicalTrials.gov (NCT00931541) AZD6088 Single Ascending Dose Study. U.S. National Institutes of Health. | |||||
| REF 40 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800028844) | |||||
| REF 41 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800009639) | |||||
| REF 42 | SDZ ENS 163, a selective muscarinic M1 receptor agonist, facilitates the induction of long-term potentiation in rat hippocampal slices. Eur J Pharmacol. 1992 Nov 3;222(1):21-5. | |||||
| REF 43 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000603) | |||||
| REF 44 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003718) | |||||
| REF 45 | Medicinal chemistry and therapeutic potential of muscarinic M3 antagonists. Med Res Rev. 2009 Nov;29(6):867-902. | |||||
| REF 46 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007055) | |||||
| REF 47 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001956) | |||||
| REF 48 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 287). | |||||
| REF 49 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001332) | |||||
| REF 50 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006926) | |||||
| REF 51 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004062) | |||||
| REF 52 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001734) | |||||
| REF 53 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006554) | |||||
| REF 54 | In vivo muscarinic cholinergic mediated effects of Lu 25-109, a M1 agonist and M2/M3 antagonist in vitro. Psychopharmacology (Berl). 1998 Jun;137(3):233-40. | |||||
| REF 55 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 334). | |||||
| REF 56 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800016553) | |||||
| REF 57 | 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. | |||||
| REF 58 | Formulation and biopharmaceutical evaluation of transdermal patch containing benztropine. Int J Pharm. 2008 Jun 5;357(1-2):55-60. | |||||
| REF 59 | Muscarinic preferential M(1) receptor antagonists enhance the discriminative-stimulus effects of cocaine in rats. Pharmacol Biochem Behav. 2007 Oct;87(4):400-4. | |||||
| REF 60 | Evaluation of in vivo binding properties of 3H-NMPB and 3H-QNB in mouse brain. J Neural Transm. 1999;106(7-8):583-92. | |||||
| REF 61 | Accidental acute clidinium toxicity. Emerg Med J. 2009 Jun;26(6):460. | |||||
| REF 62 | Capillary gas chromatography of trihexyphenidyl, procyclidine and cycrimine in biological fluids. J Chromatogr. 1989 Sep 29;494:135-42. | |||||
| REF 63 | [Characterization of muscarinic receptors in undifferentiated thyroid cells in Fisher rats]. Endocrinol Nutr. 2009 Mar;56(3):106-11. | |||||
| REF 64 | Fustin flavonoid attenuates beta-amyloid (1-42)-induced learning impairment. J Neurosci Res. 2009 Dec;87(16):3658-70. | |||||
| REF 65 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. | |||||
| REF 66 | Autonomic cardiovascular control during a novel pharmacologic alternative to ganglionic blockade. Clin Pharmacol Ther. 2008 May;83(5):692-701. | |||||
| REF 67 | A pharmacological profile of glycopyrrolate: interactions at the muscarinic acetylcholine receptor. Gen Pharmacol. 1992 Nov;23(6):1165-70. | |||||
| REF 68 | Roles of the M1 muscarinic acetylcholine receptor subtype in the regulation of basal ganglia function and implications for the treatment of Parkinson's disease.J Pharmacol Exp Ther.2012 Mar;340(3):595-603. | |||||
| REF 69 | Ultraviolet spectroscopic estimation of microenvironments and bitter tastes of oxyphenonium bromide in cyclodextrin solutions. J Pharm Sci. 1999 Aug;88(8):759-62. | |||||
| REF 70 | The effect of muscarinic receptor blockers on non-specific bronchial reactivity in patients with bronchial asthma. Pneumonol Alergol Pol. 1992;60(11-12):32-6. | |||||
| REF 71 | Demonstration of bladder selective muscarinic receptor binding by intravesical oxybutynin to treat overactive bladder. J Urol. 2004 Nov;172(5 Pt 1):2059-64. | |||||
| REF 72 | The role of M1 muscarinic cholinergic receptors in the discriminative stimulus properties of N-desmethylclozapine and the atypical antipsychotic dr... Psychopharmacology (Berl). 2009 Apr;203(2):295-301. | |||||
| REF 73 | Clinical pipeline report, company report or official report of GlaxoSmithKline (2009). | |||||
| REF 74 | Effects of nebracetam (WEB 1881 FU), a novel nootropic, as a M1-muscarinic agonist. Jpn J Pharmacol. 1991 Jan;55(1):177-80. | |||||
| REF 75 | Enantiomers of oxybutynin: in vitro pharmacological characterization at M1, M2 and M3 muscarinic receptors and in vivo effects on urinary bladder contraction, mydriasis and salivary secretion in guinea pigs. J Pharmacol Exp Ther. 1991 Feb;256(2):562-7. | |||||
| REF 76 | Clinical pipeline report, company report or official report of FemmePharma. | |||||
| REF 77 | N-desmethylclozapine, a major metabolite of clozapine, increases cortical acetylcholine and dopamine release in vivo via stimulation of M1 muscarin... Neuropsychopharmacology. 2005 Nov;30(11):1986-95. | |||||
| REF 78 | Pharmacological comparison of muscarinic ligands: historical versus more recent muscarinic M1-preferring receptor agonists. Eur J Pharmacol. 2009 Mar 1;605(1-3):53-6. | |||||
| REF 79 | On the unique binding and activating properties of xanomeline at the M1 muscarinic acetylcholine receptor. Mol Pharmacol. 1998 Jun;53(6):1120-30. | |||||
| REF 80 | Phase I clinical trial of muscarinic agonist (AC-262271) for treating glaucoma. Acadia Pharmaceuticals. | |||||
| REF 81 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
| REF 82 | Evaluation of an Innovative Population Pharmacokinetic-Based Design for Behavioral Pharmacodynamic Endpoints. AAPS J. 2012 December; 14(4): 657-663. | |||||
| REF 83 | The processing of the selective M1 agonist CDD-0102-J by human hepatic drug metabolizing enzymes. Am J Ther. 2005 Jul-Aug;12(4):300-5. | |||||
| REF 84 | Effect of telenzepine, an M1-selective muscarinic receptor antagonist, in patients with nocturnal asthma. Pulm Pharmacol. 1994 Apr;7(2):91-7. | |||||
| REF 85 | Pharmacokinetics and central nervous system toxicity of declopramide (3-chloroprocainamide) in rats and mice. Anticancer Drugs. 1999 Jan;10(1):79-88. | |||||
| REF 86 | Memory-related task performance by aged rhesus monkeys administered the muscarinic M(1)-preferring agonist, talsaclidine. Psychopharmacology (Berl). 2002 Jul;162(3):292-300. | |||||
| REF 87 | 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. | |||||
| REF 88 | Influence of the cholinergic agonist SDZ 210-086 on sleep in healthy subjects. Neuropsychopharmacology. 1993 Nov;9(3):225-32. | |||||
| REF 89 | Himbacine analogs as muscarinic receptor antagonists--effects of tether and heterocyclic variations. Bioorg Med Chem Lett. 2004 Aug 2;14(15):3967-70. | |||||
| REF 90 | 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. | |||||
| REF 91 | 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. | |||||
| REF 92 | Urea and 2-imidazolidone derivatives of the muscarinic agents oxotremorine and N-methyl-N-(1-methyl-4-pyrrolidino-2-butynyl)acetamide. J Med Chem. 1992 Aug 21;35(17):3270-9. | |||||
| REF 93 | 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. | |||||
| REF 94 | Design of dual acting anticonvulsant-antimuscarinic succinimide and hydantoin derivatives, Bioorg. Med. Chem. Lett. 7(8):979-984 (1997). | |||||
| REF 95 | 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. | |||||
| REF 96 | Cholinergic agents: aldehyde, ketone, and oxime analogues of the muscarinic agonist UH5, Bioorg. Med. Chem. Lett. 2(8):803-808 (1992). | |||||
| REF 97 | Synthesis and muscarinic activities of quinuclidin-3-yltriazole and -tetrazole derivatives. J Med Chem. 1992 Apr 3;35(7):1280-90. | |||||
| REF 98 | 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. | |||||
| REF 99 | Discovery of N-{1-[3-(3-oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4-yl}-2-phenylacetamide (Lu AE51090): an allosteric muscarinic M1 rec... J Med Chem. 2010 Sep 9;53(17):6386-97. | |||||
| REF 100 | 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. | |||||
| REF 101 | 6beta-Acetoxynortropane: a potent muscarinic agonist with apparent selectivity toward M2-receptors. J Med Chem. 1998 Jun 4;41(12):2047-55. | |||||
| REF 102 | 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. | |||||
| REF 103 | 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. | |||||
| REF 104 | On the use of nonfluorescent dye labeled ligands in FRET-based receptor binding studies. J Med Chem. 2005 Dec 1;48(24):7847-59. | |||||
| REF 105 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5436). | |||||
| REF 106 | A novel and selective class of azabicyclic muscarinic agonists incorporating an N-methoxy imidoyl halide or nitrile functionality, Bioorg. Med. Chem. Lett. 2(8):791-796 (1992). | |||||
| REF 107 | Muscarinic receptor binding profile of para-substituted caramiphen analogues. J Med Chem. 1991 Oct;34(10):2984-9. | |||||
| REF 108 | Synthesis, absolute configuration, conformational analysis and binding affinity properties of enantiomeric forms of DAU 5750, a novel M1-M3 muscari... Bioorg Med Chem. 1994 Dec;2(12):1375-83. | |||||
| REF 109 | Doi: 10.1038/bjp.2008.208 | |||||
| REF 110 | Characterization of muscarinic receptors in guinea-pig uterus. Eur J Pharmacol. 1993 Dec 7;250(2):223-30. | |||||
| REF 111 | 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. | |||||
| REF 112 | Design and synthesis of a fluorescent muscarinic antagonist. Bioorg Med Chem Lett. 2008 Jan 15;18(2):825-7. | |||||
| REF 113 | 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. | |||||
| REF 114 | Hexocyclium derivatives with a high selectivity for smooth muscle muscarinic receptors. Br J Pharmacol. 1990 May;100(1):150-2. | |||||
| REF 115 | Chloro-substituted, sterically hindered 5,11-dicarbo analogues of clozapine as potential chiral antipsychotic agents. J Med Chem. 1990 Feb;33(2):809-14. | |||||
| REF 116 | 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. | |||||
| REF 117 | Characterization of novel selective H1-antihistamines for clinical evaluation in the treatment of insomnia. J Med Chem. 2009 Sep 10;52(17):5307-10. | |||||
| REF 118 | Heterocyclic muscarinic agonists. Synthesis and biological activity of some bicyclic sulfonium arecoline bioisosteres. J Med Chem. 1988 Jul;31(7):1312-6. | |||||
| REF 119 | Structure and selectivity engineering of the M(1) muscarinic receptor toxin complex. Science. 2020 Jul 10;369(6500):161-167. | |||||
| REF 120 | Crystal structures of the M1 and M4 muscarinic acetylcholine receptors. Nature. 2016 Mar 17;531(7594):335-40. | |||||
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