Property Summary

NCBI Gene PubMed Count 107
Grant Count 19
R01 Count 16
Funding $1,487,892.42
PubMed Score 135.94
PubTator Score 322.66

Knowledge Summary

Patent (30,541)

TINX Plot

  Disease Relevance (62)

Disease Z-score Confidence
Schizophrenia 501 3.911 2.0
Allergic rhinitis 91
Arteriosclerotic Parkinsonism 8
Biliary dyskinesia 7
Bladder muscle dysfunction - overactive 4
Brain Ischemia 87
Cholinesterase Inhibitors Toxicity 4
Chronic gastritis 5
Chronic obstructive lung disease 6
Common cold 63
Cough 21
Cycloplegia 13
Dilated pupil 6
Dysuria 24
Enterocolitis 4
Epilepsy 346
Excessive salivation 5
Extrapyramidal disease 8
Gastric ulcer 34
Gastrointestinal Radiography Adjunct 11
General anesthesia 53
Increased Urinary Frequency 11
Iridocyclitis 12
Irritable bowel syndrome 59
Memory Disorders 36
Motion sickness 32
Muscarine Toxicity 3
Nasal congestion 24
Nasal discharge 26
Neurogenic bladder 16
Parkinson's disease 364
Parkinsonism 19
Peptic ulcer 22
Perioperative Mydriasis 3
Postencephalitic parkinsonism 12
Posterior synechiae 1
Prevention of Motion Sickness 3
Prevention of Post-Operative Nausea and ... 14 
Prevention of Posterior Synechiae 4
Seizures 95
Sinus bradycardia 3
Urge incontinence of urine 3
Urgent desire to urinate 11
Urinary Tract Irritation 24
Urinary incontinence 13
Uveitis 103
Vagal Reflex Bradycardia 5
Vasomotor rhinitis 15
Vertigo 3
Xerostomia Secondary to Sjogren's Syndro... 2 
astrocytoma 1,493
atypical teratoid / rhabdoid tumor 4,369
diabetes mellitus 1,663
ependymoma 2,514
glioblastoma multiforme 347
medulloblastoma 1,524
medulloblastoma, large-cell 6,234
oligodendroglioma 2,849
pediatric high grade glioma 2,712
pilocytic astrocytoma 3,086
primitive neuroectodermal tumor 3,031
psoriasis 6,685

Expression

  Differential Expression (12)

Disease log2 FC p
astrocytoma -2.600 0.000
ependymoma -2.500 0.000
oligodendroglioma -2.500 0.000
glioblastoma multiforme -2.900 0.000
medulloblastoma -3.000 0.000
atypical teratoid / rhabdoid tumor -3.000 0.000
medulloblastoma, large-cell -2.800 0.003
primitive neuroectodermal tumor -2.800 0.000
diabetes mellitus 1.200 0.001
pediatric high grade glioma -2.000 0.003
pilocytic astrocytoma -1.600 0.015
psoriasis -2.000 0.000

MLP Assay (26)

AID Type Active / Inconclusive / Inactive Description
1788 other 0 / 0 / 0 Discovery of novel allosteric modulators of the M1 muscarinic receptor: Agonist Ancillary Activity
1921 other 2 / 0 / 0 Discovery of a Highly Selective in vitro and in vivo M4 Positive Allosteric Modulator: Ancillary Activity
435021 other 20 / 0 / 21 Discovery of novel allosteric modulators of the M1 muscarinic receptor: Antagonist Activity for Analogs
588744 confirmatory 1 / 0 / 8 Human M1 PAM Extended Characterization CounterScreen (CRC)
588814 screening 1190 / 0 / 358294 Fluorescence-based cell-based primary high throughput screening assay to identify agonists of the human cholinergic receptor, muscarinic 1 (CHRM1)
588816 summary 0 / 0 / 0 Summary of the probe development efforts to identify agonists of the human cholinergic receptor, muscarinic 1 (CHRM1)
588819 screening 316 / 0 / 359168 Fluorescence-based cell-based primary high throughput screening assay to identify positive allosteric modulators (PAMs) of the human M1 muscarinic receptor (CHRM1).
588852 screening 4560 / 0 / 354924 Fluorescence-based cell-based primary high throughput screening assay to identify antagonists of the human M1 muscarinic receptor (CHRM1)
623924 confirmatory 1 / 0 / 9 Chemical optimization of in vitro pharmacology and DMPK properties of the highly selective mAChR 4 (M4) Positive Allosteric Modulator (PAM) Series with Greatly Improved Human Receptor Activity (hM1 CounterScreen)
624355 other 0 / 0 / 0 Late stage results from the probe development efforts to identify dual inhibitors of signal transducer and activator of transcription 3 (STAT3) and nuclear factor NF-kappa-B (NF-kB): Cell-based radioligand binding assay to determine the binding affinities for selected transporters, receptors, and GPCRs
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Gene RIF (78)

PMID Text
26958838 crystal structures of the M1 and M4 muscarinic receptors bound to the inverse agonist, tiotropium
26481978 The rs2067477 muscarinic M1 receptor genotype is associated with grey matter volume in schizophrenia.
25326383 this study highlights how the properties of affinity and cooperativity can be differentially modified on a common structural scaffold and identifies molecular features that can be exploited to tailor the development of M1 mAChR-targeting PAMs.
24821386 changes in membrane cholesterol concentration differentially impact preferential and non-preferential M1 and M3 receptor signaling
24753247 We show that BQCA potentiates agonist-induced beta-arrestin recruitment to M1 mAChRs.
24636402 In patients with schizophrenia, both cell body staining and elevated M1 muscarinic receptor reactivity correlated with higher symptom scores.
24443568 Mutation of amino acid residues that form the orthosteric binding pocket caused a loss of carbachol response that could be rescued by BQCA.
24430298 CHRM2 but not CHRM1 or CHRM3 polymorphisms are associated with asthma susceptibility in Mexican patients.
24365239 demonstrate that activation of M1 muscarinic acetylcholine receptor augments the restitution of epithelial barrier function in T84 cell monolayers after ethanol-induced epithelial injury, via ERK-dependent phosphorylation of focal adhesion kinase
24292102 the levels were comparable for complexes containing GluR2, GluR3 and GluR4 as well as 5-HT1A. Moreover, the levels of complexes containing muscarinic AChR M1, NR1 and GluR1 were significantly increased in male patients with AD.
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AA Sequence

MNTSAPPAVSPNITVLAPGKGPWQVAFIGITTGLLSLATVTGNLLVLISFKVNTELKTVNNYFLLSLACA      1 - 70
DLIIGTFSMNLYTTYLLMGHWALGTLACDLWLALDYVASNASVMNLLLISFDRYFSVTRPLSYRAKRTPR     71 - 140
RAALMIGLAWLVSFVLWAPAILFWQYLVGERTVLAGQCYIQFLSQPIITFGTAMAAFYLPVTVMCTLYWR    141 - 210
IYRETENRARELAALQGSETPGKGGGSSSSSERSQPGAEGSPETPPGRCCRCCRAPRLLQAYSWKEEEEE    211 - 280
DEGSMESLTSSEGEEPGSEVVIKMPMVDPEAQAPTKQPPRSSPNTVKRPTKKGRDRAGKGQKPRGKEQLA    281 - 350
KRKTFSLVKEKKAARTLSAILLAFILTWTPYNIMVLVSTFCKDCVPETLWELGYWLCYVNSTINPMCYAL    351 - 420
CNKAFRDTFRLLLLCRWDKRRWRKIPKRPGSVHRTPSRQC                                  421 - 460
//

Text Mined References (108)

PMID Year Title
26958838 2016 Crystal structures of the M1 and M4 muscarinic acetylcholine receptors.
26481978 2015 The effect of a muscarinic receptor 1 gene variant on grey matter volume in schizophrenia.
25326383 2014 Mechanistic insights into allosteric structure-function relationships at the M1 muscarinic acetylcholine receptor.
24821386 2015 Changes in Membrane Cholesterol Differentially Influence Preferential and Non-preferential Signaling of the M1 and M3 Muscarinic Acetylcholine Receptors.
24753247 2014 Allosteric modulation of M1 muscarinic acetylcholine receptor internalization and subcellular trafficking.
24636402 2014 Elevated levels of autoantibodies targeting the M1 muscarinic acetylcholine receptor and neurofilament medium in sera from subgroups of patients with schizophrenia.
24443568 2014 Molecular determinants of allosteric modulation at the M1 muscarinic acetylcholine receptor.
24430298 2014 CHRM2 but not CHRM1 or CHRM3 polymorphisms are associated with asthma susceptibility in Mexican patients.
24365239 2014 Activation of focal adhesion kinase via M1 muscarinic acetylcholine receptor is required in restitution of intestinal barrier function after epithelial injury.
24292102 2014 Changes of several brain receptor complexes in the cerebral cortex of patients with Alzheimer disease: probable new potential pharmaceutical targets.
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