Target Information
| Target General Information | Top | |||||
|---|---|---|---|---|---|---|
| Target ID |
T79961
(Former ID: TTDI01755)
|
|||||
| Target Name |
Muscarinic acetylcholine receptor M5 (CHRM5)
|
|||||
| Synonyms |
CHRM5
Click to Show/Hide
|
|||||
| Gene Name |
CHRM5
|
|||||
| Target Type |
Successful target
|
[1] | ||||
| Disease | [+] 28 Target-related Diseases | + | ||||
| 1 | Abnormal micturition [ICD-11: MF50] | |||||
| 2 | Anterior uveitis [ICD-11: 9A96] | |||||
| 3 | Appearance/behaviour symptom [ICD-11: MB23] | |||||
| 4 | Asthma [ICD-11: CA23] | |||||
| 5 | Brain disease [ICD-11: 8C70-8E61] | |||||
| 6 | Central and peripheral nervous disease [ICD-11: 8A04-8E7Z] | |||||
| 7 | Chronic obstructive pulmonary disease [ICD-11: CA22] | |||||
| 8 | Cognition symptoms/signs/clinical sympton [ICD-11: MB21] | |||||
| 9 | Cough [ICD-11: MD12] | |||||
| 10 | Digestive system disease [ICD-11: DE2Z] | |||||
| 11 | Female pelvic pain [ICD-11: GA34] | |||||
| 12 | Functional bladder disorder [ICD-11: GC50] | |||||
| 13 | Gastritis [ICD-11: DA42] | |||||
| 14 | General examination [ICD-11: QA00] | |||||
| 15 | Glaucoma [ICD-11: 9C61] | |||||
| 16 | Hypertension [ICD-11: BA00-BA04] | |||||
| 17 | Infectious gastroenteritis/colitis [ICD-11: 1A40] | |||||
| 18 | Irritable bowel syndrome [ICD-11: DD91] | |||||
| 19 | Nystagmus [ICD-11: 9C84] | |||||
| 20 | Oesophagus motility disorder [ICD-11: DA21] | |||||
| 21 | Pain [ICD-11: MG30-MG3Z] | |||||
| 22 | Pancreatitis [ICD-11: DC31-DC34] | |||||
| 23 | Parkinsonism [ICD-11: 8A00] | |||||
| 24 | Peptic ulcer [ICD-11: DA61] | |||||
| 25 | Polyuria [ICD-11: MF55] | |||||
| 26 | Tonus and reflex abnormality [ICD-11: MB47] | |||||
| 27 | Unspecific substance harmful effect [ICD-11: NE6Z] | |||||
| 28 | Urgency [ICD-11: N.A.] | |||||
| 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.
Click to Show/Hide
|
|||||
| BioChemical Class |
GPCR rhodopsin
|
|||||
| UniProt ID | ||||||
| Sequence |
MEGDSYHNATTVNGTPVNHQPLERHRLWEVITIAAVTAVVSLITIVGNVLVMISFKVNSQ
LKTVNNYYLLSLACADLIIGIFSMNLYTTYILMGRWALGSLACDLWLALDYVASNASVMN LLVISFDRYFSITRPLTYRAKRTPKRAGIMIGLAWLISFILWAPAILCWQYLVGKRTVPL DECQIQFLSEPTITFGTAIAAFYIPVSVMTILYCRIYRETEKRTKDLADLQGSDSVTKAE KRKPAHRALFRSCLRCPRPTLAQRERNQASWSSSRRSTSTTGKPSQATGPSANWAKAEQL TTCSSYPSSEDEDKPATDPVLQVVYKSQGKESPGEEFSAEETEETFVKAETEKSDYDTPN YLLSPAAAHRPKSQKCVAYKFRLVVKADGNQETNNGCHKVKIMPCPFPVAKEPSTKGLNP NPSHQMTKRKRVVLVKERKAAQTLSAILLAFIITWTPYNIMVLVSTFCDKCVPVTLWHLG YWLCYVNSTVNPICYALCNRTFRKTFKMLLLCRWKKKKVEEKLYWQGNSKLP Click to Show/Hide
|
|||||
| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Approved Drug(s) | [+] 31 Approved Drugs | + | ||||
| 1 | ACECLIDINE | Drug Info | Approved | Glaucoma/ocular hypertension | [2], [3] | |
| 2 | Anisodine | Drug Info | Approved | Central and peripheral nervous disease | [3] | |
| 3 | Anisotropine Methylbromide | Drug Info | Approved | Peptic ulcer | [3], [4] | |
| 4 | Atropine | Drug Info | Approved | Organophosphate poisoning | [5], [6] | |
| 5 | Belladonna | Drug Info | Approved | Colitis | [3] | |
| 6 | Bethanechol | Drug Info | Approved | Urinary retention | [7], [8] | |
| 7 | Butylscopolamine | Drug Info | Approved | Dysmenorrhea | [3] | |
| 8 | Choline alfoscerate | Drug Info | Approved | Amnesia | [3] | |
| 9 | Cimetropium bromide | Drug Info | Approved | Spasm | [3] | |
| 10 | Cryptenamine Acetates | Drug Info | Approved | Hypertension | [3] | |
| 11 | Cyclopentolate | Drug Info | Approved | Examination of eyes or vision | [3] | |
| 12 | Emepronium | Drug Info | Approved | Urinary incontinence | [3] | |
| 13 | Flavoxate | Drug Info | Approved | Suprapubic pain | [3] | |
| 14 | Flutropium bromide | Drug Info | Approved | Cough | [3] | |
| 15 | Homatropine Methylbromide | Drug Info | Approved | Uveitis | [3], [9] | |
| 16 | Hyoscyamine | Drug Info | Approved | Gastrointestinal disease | [10] | |
| 17 | Ispaghula | Drug Info | Approved | Irritable bowel syndrome | [10] | |
| 18 | Mebeverine | Drug Info | Approved | Irritable bowel syndrome | [10] | |
| 19 | Mepenzolate | Drug Info | Approved | Gastrointestinal disease | [3], [11] | |
| 20 | Methantheline | Drug Info | Approved | Gastritis | [3] | |
| 21 | Oxitropium bromide | Drug Info | Approved | Asthma | [3] | |
| 22 | Oxyphencyclimine | Drug Info | Approved | Peptic ulcer | [3], [12], [13] | |
| 23 | Pilocarpine | Drug Info | Approved | Glaucoma/ocular hypertension | [14], [15] | |
| 24 | Prifinium | Drug Info | Approved | Irritable bowel syndrome | [3] | |
| 25 | Procyclidine | Drug Info | Approved | Parkinson disease | [16], [17] | |
| 26 | Promazine | Drug Info | Approved | Psychomotor agitation | [3] | |
| 27 | Propiverine | Drug Info | Approved | Urinary incontinence | [3] | |
| 28 | Tridihexethyl | Drug Info | Approved | Acquired nystagmus | [18] | |
| 29 | Trospium | Drug Info | Approved | Spasm | [3], [19], [20], [21], [22] | |
| 30 | Umeclidinium | Drug Info | Approved | Chronic obstructive pulmonary disease | [23], [24] | |
| 31 | Pramiracetam | Drug Info | Approved (orphan drug) | Brain disease | [3] | |
| Clinical Trial Drug(s) | [+] 4 Clinical Trial Drugs | + | ||||
| 1 | L-651582 | Drug Info | Phase 3 | Solid tumour/cancer | [25] | |
| 2 | OrM3 | Drug Info | Phase 2b | Chronic obstructive pulmonary disease | [26] | |
| 3 | GSK233705 | Drug Info | Phase 2 | Chronic obstructive pulmonary disease | [26] | |
| 4 | Dexpirronium | Drug Info | Phase 1 | Chronic obstructive pulmonary disease | [27] | |
| Discontinued Drug(s) | [+] 7 Discontinued Drugs | + | ||||
| 1 | Benactyzine | Drug Info | Withdrawn from market | Depression | [28] | |
| 2 | BMS-181168 | Drug Info | Discontinued in Phase 2 | Cognitive impairment | [29] | |
| 3 | DDP-200 | Drug Info | Discontinued in Phase 2 | Urinary incontinence | [30] | |
| 4 | FK-584 | Drug Info | Discontinued in Phase 2 | Central and peripheral nervous disease | [31] | |
| 5 | AM-831 | Drug Info | Discontinued in Phase 1 | Schizophrenia | [32] | |
| 6 | RS 86 | Drug Info | Terminated | Alzheimer disease | [34] | |
| 7 | SU-740 | Drug Info | Terminated | Stomach ulcer | [35] | |
| Preclinical Drug(s) | [+] 1 Preclinical Drugs | + | ||||
| 1 | Org-23366 | Drug Info | Preclinical | Schizophrenia | [33] | |
| Mode of Action | [+] 6 Modes of Action | + | ||||
| Inhibitor | [+] 30 Inhibitor drugs | + | ||||
| 1 | ACECLIDINE | Drug Info | [36] | |||
| 2 | 1'-Benzyl-3-phenyl-[3,4']bipiperidinyl-2,6-dione | Drug Info | [73] | |||
| 3 | 1-Methyl-1-(4-pyrrolidin-1-yl-but-2-ynyl)-urea | Drug Info | [74] | |||
| 4 | 2,8-Dimethyl-1-oxa-8-aza-spiro[4.5]decan-3-one | Drug Info | [75] | |||
| 5 | 2-Methyl-6-pyrrolidin-1-yl-hex-4-ynal oxime | Drug Info | [76] | |||
| 6 | 3-(3-benzylamino)-piperidin-2-one | Drug Info | [77] | |||
| 7 | 3-Methyl-7-pyrrolidin-1-yl-hept-5-yn-2-one | Drug Info | [76] | |||
| 8 | 3-Tetrazol-2-yl-1-aza-bicyclo[2.2.2]octane | Drug Info | [78] | |||
| 9 | 4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one | Drug Info | [79] | |||
| 10 | 6-Dimethylamino-2-methyl-hex-4-ynal oxime | Drug Info | [76] | |||
| 11 | 7-Dimethylamino-3-methyl-hept-5-yn-2-one | Drug Info | [76] | |||
| 12 | 7-Dimethylamino-hept-5-yn-2-one | Drug Info | [76] | |||
| 13 | 7-Pyrrolidin-1-yl-hept-5-yn-2-one | Drug Info | [76] | |||
| 14 | Acetic acid 8-aza-bicyclo[3.2.1]oct-6-yl ester | Drug Info | [81] | |||
| 15 | Benzoic acid 8-aza-bicyclo[3.2.1]oct-6-yl ester | Drug Info | [81] | |||
| 16 | BRL-55473 | Drug Info | [83] | |||
| 17 | Cremastrine | Drug Info | [84] | |||
| 18 | FLUMEZAPINE | Drug Info | [85] | |||
| 19 | FM1-10 | Drug Info | [86] | |||
| 20 | FM1-43 | Drug Info | [86] | |||
| 21 | GNF-PF-5618 | Drug Info | [87] | |||
| 22 | ISOCLOZAPINE | Drug Info | [88] | |||
| 23 | ISOLOXAPINE | Drug Info | [89] | |||
| 24 | N-(4-Dimethylamino-but-2-ynyl)-N-methyl-acetamide | Drug Info | [76] | |||
| 25 | N-methoxyquinuclidine-3-carboximidoyl chloride | Drug Info | [83] | |||
| 26 | N-methoxyquinuclidine-3-carboximidoyl fluoride | Drug Info | [83] | |||
| 27 | PF-3409409 | Drug Info | [91] | |||
| 28 | SULFOARECOLINE | Drug Info | [92] | |||
| 29 | VU0119498 | Drug Info | [93] | |||
| 30 | VU0238429 | Drug Info | [93] | |||
| Modulator | [+] 21 Modulator drugs | + | ||||
| 1 | Anisodine | Drug Info | [37] | |||
| 2 | Belladonna | Drug Info | [43], [3] | |||
| 3 | Butylscopolamine | Drug Info | [47], [3] | |||
| 4 | Choline alfoscerate | Drug Info | [48] | |||
| 5 | Cimetropium bromide | Drug Info | [49], [50] | |||
| 6 | Cryptenamine Acetates | Drug Info | [51] | |||
| 7 | Emepronium | Drug Info | [53], [3] | |||
| 8 | Flutropium bromide | Drug Info | [49] | |||
| 9 | Oxitropium bromide | Drug Info | [49] | |||
| 10 | Pramiracetam | Drug Info | [1], [3] | |||
| 11 | Prifinium | Drug Info | [62], [3] | |||
| 12 | Umeclidinium | Drug Info | [23] | |||
| 13 | L-651582 | Drug Info | [25] | |||
| 14 | BMS-181168 | Drug Info | [67] | |||
| 15 | DDP-200 | Drug Info | [68] | |||
| 16 | FK-584 | Drug Info | [69] | |||
| 17 | SU-740 | Drug Info | [72] | |||
| 18 | BHT-3034 | Drug Info | [48] | |||
| 19 | CRTX-070 | Drug Info | [48] | |||
| 20 | JWB-1-84-1 | Drug Info | [48] | |||
| 21 | Recombinant botulinum toxin | Drug Info | [48] | |||
| Binder | [+] 4 Binder drugs | + | ||||
| 1 | Anisotropine Methylbromide | Drug Info | [38] | |||
| 2 | Oxyphencyclimine | Drug Info | [59] | |||
| 3 | Promazine | Drug Info | [64] | |||
| 4 | Tridihexethyl | Drug Info | [66] | |||
| Antagonist | [+] 21 Antagonist drugs | + | ||||
| 1 | Atropine | Drug Info | [39], [40], [41], [42] | |||
| 2 | Cyclopentolate | Drug Info | [52] | |||
| 3 | Flavoxate | Drug Info | [54] | |||
| 4 | Homatropine Methylbromide | Drug Info | [55] | |||
| 5 | Hyoscyamine | Drug Info | [56] | |||
| 6 | Ispaghula | Drug Info | [10] | |||
| 7 | Mebeverine | Drug Info | [10] | |||
| 8 | Mepenzolate | Drug Info | [57] | |||
| 9 | Methantheline | Drug Info | [58] | |||
| 10 | Procyclidine | Drug Info | [63] | |||
| 11 | Propiverine | Drug Info | [65], [3] | |||
| 12 | Trospium | Drug Info | [55] | |||
| 13 | OrM3 | Drug Info | [26] | |||
| 14 | GSK233705 | Drug Info | [26] | |||
| 15 | Dexpirronium | Drug Info | [48] | |||
| 16 | Benactyzine | Drug Info | [42] | |||
| 17 | Org-23366 | Drug Info | [33] | |||
| 18 | alpha-conotoxin AuIB | Drug Info | [48] | |||
| 19 | alpha-conotoxin GI | Drug Info | [48] | |||
| 20 | alpha-conotoxin PnIA | Drug Info | [48] | |||
| 21 | Aprophen | Drug Info | [42], [82] | |||
| Agonist | [+] 7 Agonist drugs | + | ||||
| 1 | Bethanechol | Drug Info | [44], [45], [46] | |||
| 2 | Pilocarpine | Drug Info | [60], [61] | |||
| 3 | AM-831 | Drug Info | [70] | |||
| 4 | RS 86 | Drug Info | [71] | |||
| 5 | Muscarine | Drug Info | [41] | |||
| 6 | [125I]epibatidine | Drug Info | [48] | |||
| 7 | [3H]cytisine | Drug Info | [48] | |||
| Blocker (channel blocker) | [+] 2 Blocker (channel blocker) drugs | + | ||||
| 1 | A-867744 | Drug Info | [80] | |||
| 2 | NS1738 | Drug Info | [90] | |||
| Cell-based Target Expression Variations | Top | |||||
|---|---|---|---|---|---|---|
| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: Tiotropium | Ligand Info | |||||
| Structure Description | Structure of the M5 muscarinic acetylcholine receptor (M5-T4L) bound to tiotropium | PDB:6OL9 | ||||
| Method | X-ray diffraction | Resolution | 2.54 Å | Mutation | No | [94] |
| PDB Sequence |
RLWEVITIAA
35 VTAVVSLITI45 VGNVLVMISF55 KVNSQLKTVN65 NYYLLSLACA75 DLIIGIFSMN 85 LYTTYILMGR95 WALGSLACDL105 WLALDYVASN115 ARVMNLLVIS125 FDRYFSITRP 135 LTYRAKRTPK145 RAGIMIGLAW155 LISFILWAPA165 ILCWQYLVGK175 RTVPLDECQI 185 QFLSEPTITF195 GTAIAAFYIP205 VSVMTILYCR215 IYRETEKRTN1001 IFEMLRIDEG 1011 LRLKIYKDTE1021 GYYTIGIGHL1031 TKDEAEKLFN1067 QDVDAAVRGI1077 LRNAKLKPVY 1087 DSLDAVRRAA1097 LINMVFQMGE1107 TGVAGFTNSL1117 RMLQQKRWDE1127 AAVNLAKSRW 1137 YNQTPNRAKR1147 VITTFRTGTW1157 DAYRVVLVKE437 RKAAQTLSAI447 LLAFIITWTP 457 YNIMVLVSTF467 CDKCVPVTLW477 HLGYWLCYVN487 STVNPICYAL497 CNRTFRKTFK 507 MLLLCR
|
|||||
|
|
||||||
| Ligand Name: Oleic acid | Ligand Info | |||||
| Structure Description | Structure of the M5 muscarinic acetylcholine receptor (M5-T4L) bound to tiotropium | PDB:6OL9 | ||||
| Method | X-ray diffraction | Resolution | 2.54 Å | Mutation | No | [94] |
| PDB Sequence |
RLWEVITIAA
35 VTAVVSLITI45 VGNVLVMISF55 KVNSQLKTVN65 NYYLLSLACA75 DLIIGIFSMN 85 LYTTYILMGR95 WALGSLACDL105 WLALDYVASN115 ARVMNLLVIS125 FDRYFSITRP 135 LTYRAKRTPK145 RAGIMIGLAW155 LISFILWAPA165 ILCWQYLVGK175 RTVPLDECQI 185 QFLSEPTITF195 GTAIAAFYIP205 VSVMTILYCR215 IYRETEKRTN1001 IFEMLRIDEG 1011 LRLKIYKDTE1021 GYYTIGIGHL1031 TKDEAEKLFN1067 QDVDAAVRGI1077 LRNAKLKPVY 1087 DSLDAVRRAA1097 LINMVFQMGE1107 TGVAGFTNSL1117 RMLQQKRWDE1127 AAVNLAKSRW 1137 YNQTPNRAKR1147 VITTFRTGTW1157 DAYRVVLVKE437 RKAAQTLSAI447 LLAFIITWTP 457 YNIMVLVSTF467 CDKCVPVTLW477 HLGYWLCYVN487 STVNPICYAL497 CNRTFRKTFK 507 MLLLCR
|
|||||
|
|
ASN115
3.387
MET119
3.658
LEU161
4.018
TRP162
3.809
PRO164
3.360
ALA165
3.699
CYS168
3.445
TRP169
3.425
LEU172
3.255
PHE187
3.865
THR197
4.675
|
|||||
| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
|---|---|
|
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).
Human Similarity Proteins
Human Pathway Affiliation
|
|
| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
|---|---|---|---|
| Calcium signaling pathway | hsa04020 | Affiliated Target |
|
| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Neuroactive ligand-receptor interaction | hsa04080 | Affiliated Target |
|
| Class: Environmental Information Processing => Signaling molecules and interaction | Pathway Hierarchy | ||
| Cholinergic synapse | hsa04725 | Affiliated Target |
|
| Class: Organismal Systems => Nervous system | Pathway Hierarchy | ||
| Regulation of actin cytoskeleton | hsa04810 | Affiliated Target |
|
| Class: Cellular Processes => Cell motility | Pathway Hierarchy | ||
| Chemical Structure based Activity Landscape of Target | Top |
|---|---|
| Drug Property Profile of Target | Top | |
|---|---|---|
| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
|
|
||
| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
|
|
||
| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
|
|
||
| "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 | |||||
|---|---|---|---|---|---|---|
| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
|---|---|---|---|---|---|---|
| Target Poor or Non Binders | ||||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| REF 1 | Some neurochemical properties of pramiracetam (CI-879), a new cognition-enhancing agent. Article first published online: 5 OCT 2004. | |||||
| 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: 288). | |||||
| REF 3 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 4 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 013428. | |||||
| 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: 320). | |||||
| REF 6 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 071295. | |||||
| REF 7 | 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: 297). | |||||
| REF 8 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 040518. | |||||
| REF 9 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 086310. | |||||
| REF 10 | Emerging drugs for irritable bowel syndrome. Expert Opin Emerg Drugs. 2006 May;11(2):293-313. | |||||
| REF 11 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 010679. | |||||
| REF 12 | 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: 7256). | |||||
| REF 13 | Drug information of Oxyphencyclimine, 2008. eduDrugs. | |||||
| REF 14 | 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: 305). | |||||
| REF 15 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 020619. | |||||
| REF 16 | 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: 7280). | |||||
| REF 17 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 009818. | |||||
| REF 18 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 009489. | |||||
| REF 19 | 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: 7480). | |||||
| REF 20 | 2004 approvals: the demise of the blockbuster. Nat Rev Drug Discov. 2005 Feb;4(2):93-4. | |||||
| REF 21 | Trospium chloride: the European experience. Expert Opin Pharmacother. 2006 Jul;7(10):1373-80. | |||||
| REF 22 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 021595. | |||||
| REF 23 | 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: 7354). | |||||
| REF 24 | Clinical pipeline report, company report or official report of GlaxoSmithKline. | |||||
| REF 25 | The antiproliferative and antimetastatic compound L651582 inhibits muscarinic acetylcholine receptor-stimulated calcium influx and arachidonic acid release. J Pharmacol Exp Ther. 1991 Jun;257(3):967-71. | |||||
| REF 26 | Emerging drugs in chronic obstructive pulmonary disease. Expert Opin Emerg Drugs. 2009 Mar;14(1):181-94. | |||||
| REF 27 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800028438) | |||||
| REF 28 | Benactyzine as an aid in treatment of anxiety states; preliminary report. Br Med J. 1957 Feb 9;1(5014):306-10. | |||||
| REF 29 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001318) | |||||
| REF 30 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800020170) | |||||
| 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 800006686) | |||||
| REF 32 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800016551) | |||||
| REF 33 | The pipeline and future of drug development in schizophrenia. Mol Psychiatry. 2007 Oct;12(10):904-22. | |||||
| REF 34 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000634) | |||||
| REF 35 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004989) | |||||
| REF 36 | 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 37 | Medicinal plants in therapy. Bull World Health Organ. 1985;63(6):965-81. | |||||
| REF 38 | Anisotropine methylbromide: a new antispasmodic for gastrointestinal disorders. Curr Ther Res Clin Exp. 1963 May;5:213-8. | |||||
| REF 39 | Additive protective effects of donepezil and nicotine against salsolinol-induced cytotoxicity in SH-SY5Y cells. Neurotox Res. 2009 Oct;16(3):194-204. | |||||
| REF 40 | Loss of M2 muscarinic receptor function inhibits development of hypoxic bradycardia and alters cardiac beta-adrenergic sensitivity in larval zebraf... Am J Physiol Regul Integr Comp Physiol. 2009 Aug;297(2):R412-20. | |||||
| REF 41 | The effects of the antagonists of muscarinic acetylcholine receptor subtypes in rat brain on urinary bladder contraction. Nippon Hinyokika Gakkai Zasshi. 2002 Mar;93(3):427-34. | |||||
| REF 42 | The muscarinic antagonists aprophen and benactyzine are noncompetitive inhibitors of the nicotinic acetylcholine receptor. Mol Pharmacol. 1987 Nov;32(5):678-85. | |||||
| REF 43 | Plasma level of atropine after accidental ingestion of Atropa belladonna. Clin Toxicol (Phila). 2009 Jul;47(6):602-4. | |||||
| REF 44 | Loss of Ca-mediated ion transport during colitis correlates with reduced ion transport responses to a Ca-activated K channel opener. Br J Pharmacol. 2009 Apr;156(7):1085-97. | |||||
| REF 45 | Morphine increases acetylcholine release in the trigeminal nuclear complex. Sleep. 2008 Dec 1;31(12):1629-37. | |||||
| REF 46 | Postoperative analgesia induced by intrathecal neostigmine or bethanechol in rats. Clin Exp Pharmacol Physiol. 2009 Jul;36(7):648-54. | |||||
| REF 47 | Comparison of pharmacological effects of L- and DL-n-butyl-scopolamine in rat uterus. Yao Xue Xue Bao. 1994;29(1):24-7. | |||||
| 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. (Target id: 467). | |||||
| REF 49 | Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. | |||||
| REF 50 | Scopolamine in Brugmansia suaveolens (Solanaceae): defense, allocation, costs, and induced response. J Chem Ecol. 2007 Feb;33(2):297-309. | |||||
| REF 51 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. | |||||
| REF 52 | High spatial resolution studies of muscarinic neuroeffector junctions in mouse isolated vas deferens. Neuroscience. 2009 Sep 15;162(4):1366-76. | |||||
| REF 53 | Classification of the presynaptic muscarinic receptor subtype that regulates 3H-acetylcholine secretion in the guinea pig urinary bladder in vitro. J Pharmacol Exp Ther. 1995 Jul;274(1):458-68. | |||||
| REF 54 | Brain pertussis toxin-sensitive G proteins are involved in the flavoxate hydrochloride-induced suppression of the micturition reflex in rats. Brain Res. 1996 Jul 15;727(1-2):91-8. | |||||
| REF 55 | Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. | |||||
| REF 56 | Reconstitution of the purified porcine atrial muscarinic acetylcholine receptor with purified porcine atrial inhibitory guanine nucleotide binding protein. Biochemistry. 1987 Dec 15;26(25):8175-82. | |||||
| REF 57 | Isolation of cholinergic active ingredients in aqueous extracts of Mareya micrantha using the longitudinal muscle of isolated guinea-pig ileum as a pharmacological activity marker. J Ethnopharmacol. 1995 Mar;45(3):215-22. | |||||
| REF 58 | Anticholinergics for urinary symptoms in multiple sclerosis. Cochrane Database Syst Rev. 2009 Jan 21;(1):CD004193. | |||||
| REF 59 | Stereoselective interaction of procyclidine, hexahydro-difenidol, hexbutinol and oxyphencyclimine, and of related antagonists, with four muscarinic receptors. Eur J Pharmacol. 1992 Sep 1;227(1):33-42. | |||||
| REF 60 | Retinoic acid prevents virus-induced airway hyperreactivity and M2 receptor dysfunction via anti-inflammatory and antiviral effects. Am J Physiol Lung Cell Mol Physiol. 2009 Aug;297(2):L340-6. | |||||
| REF 61 | Muscarinic activation attenuates abnormal processing of beta-amyloid precursor protein induced by cobalt chloride-mimetic hypoxia in retinal gangli... Biochem Biophys Res Commun. 2009 Jun 19;384(1):110-3. | |||||
| REF 62 | Ligand binding properties of muscarinic acetylcholine receptor subtypes (m1-m5) expressed in baculovirus-infected insect cells. J Pharmacol Exp Ther. 1995 Jul;274(1):378-84. | |||||
| REF 63 | Protection against soman-induced seizures in rats: relationship among doses of prophylactics, soman, and adjuncts. Toxicol Appl Pharmacol. 2004 May 1;196(3):327-36. | |||||
| REF 64 | Muscarinic cholinergic and histamine H1 receptor binding of phenothiazine drug metabolites. Life Sci. 1988;43(5):405-12. | |||||
| REF 65 | Affinity profiles of various muscarinic antagonists for cloned human muscarinic acetylcholine receptor (mAChR) subtypes and mAChRs in rat heart and submandibular gland. Life Sci. 1999;64(25):2351-8. | |||||
| REF 66 | Effect of anticholinergic agents upon acquired nystagmus: a double-blind study of trihexyphenidyl and tridihexethyl chloride. Neurology. 1991 Nov;41(11):1737-41. | |||||
| REF 67 | Efficacy and safety of BMY 21,502 in Alzheimer disease. Ann Pharmacother. 1996 Dec;30(12):1376-80. | |||||
| REF 68 | CA patent application no. 753057, Sustained release oral dosage forms of an r-baclofen prodrug. | |||||
| REF 69 | US patent application no. 2005,0261,328, Pharmaceutical composition comprising beta-3-adrenoceptor-agonists and antimuscarinic agents. | |||||
| REF 70 | Clinical pipeline report, company report or official report of Avarx. | |||||
| REF 71 | The pharmacological assessment of RS 86 (2-ethyl-8-methyl-2,8-diazaspiro-[4,5]-decan-1,3-dion hydrobromide). A potent, specific muscarinic acetylcholine receptor agonist. Eur J Pharmacol. 1986 Jun 5;125(1):45-62. | |||||
| REF 72 | SU-840, a novel synthetic flavonoid derivative of sophoradin, with potent gastroprotective and ulcer healing activity. Journal of physiology and pharmacology. 49:1 1998 Mar pg 83-98 | |||||
| REF 73 | 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 74 | 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 75 | 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 76 | Cholinergic agents: aldehyde, ketone, and oxime analogues of the muscarinic agonist UH5, Bioorg. Med. Chem. Lett. 2(8):803-808 (1992). | |||||
| REF 77 | 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 78 | Synthesis and muscarinic activities of quinuclidin-3-yltriazole and -tetrazole derivatives. J Med Chem. 1992 Apr 3;35(7):1280-90. | |||||
| REF 79 | 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 80 | In vitro pharmacological characterization of a novel allosteric modulator of alpha 7 neuronal acetylcholine receptor, 4-(5-(4-chlorophenyl)-2-methy... J Pharmacol Exp Ther. 2009 Jul;330(1):257-67. | |||||
| REF 81 | 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 82 | M1 muscarinic antagonists interact with sigma recognition sites. Life Sci. 1991;49(17):1229-35. | |||||
| REF 83 | 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 84 | Cremastrine, a pyrrolizidine alkaloid from Cremastra appendiculata. J Nat Prod. 2005 Apr;68(4):572-3. | |||||
| REF 85 | 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 86 | Design and synthesis of a fluorescent muscarinic antagonist. Bioorg Med Chem Lett. 2008 Jan 15;18(2):825-7. | |||||
| REF 87 | 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 88 | 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 89 | 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 90 | An allosteric modulator of the alpha7 nicotinic acetylcholine receptor possessing cognition-enhancing properties in vivo. J Pharmacol Exp Ther. 2007 Oct;323(1):294-307. | |||||
| REF 91 | Design, synthesis and evaluation of N-[(3S)-pyrrolidin-3-yl]benzamides as selective noradrenaline reuptake inhibitors: CNS penetration in a more po... Bioorg Med Chem Lett. 2009 Aug 15;19(16):4579-83. | |||||
| REF 92 | Heterocyclic muscarinic agonists. Synthesis and biological activity of some bicyclic sulfonium arecoline bioisosteres. J Med Chem. 1988 Jul;31(7):1312-6. | |||||
| REF 93 | Discovery of the first highly M5-preferring muscarinic acetylcholine receptor ligand, an M5 positive allosteric modulator derived from a series of ... J Med Chem. 2009 Jun 11;52(11):3445-8. | |||||
| REF 94 | Crystal structure of the M(5) muscarinic acetylcholine receptor. Proc Natl Acad Sci U S A. 2019 Dec 17;116(51):26001-26007. | |||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.