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Discovery and optimization of a novel series of highly CNS penetrant M4 PAMs based on a 5,6-dimethyl-4-(piperidin-1-yl)thieno[2,3-d]pyrimidine core.
Wood MR, Noetzel MJ, Engers JL, Bollinger KA, Melancon BJ, Tarr JC, Han C, West M, Gregro AR, Lamsal A, Chang S, Ajmera S, Smith E, Chase P, Hodder PS, Bubser M, Jones CK, Hopkins CR, Emmitte KA, Niswender CM, Wood MW, Duggan ME, Conn PJ, Bridges TM, Lindsley CW
(2016) Bioorg Med Chem Lett 26: 3029-3033
MeSH Terms: Allosteric Regulation, Animals, Brain, Humans, Microsomes, Liver, Piperidines, Pyrimidines, Quinazolines, Rats, Receptor, Muscarinic M4, Structure-Activity Relationship, Thiophenes
Added April 6, 2017
0 Communities
3 Members
0 Resources
12 MeSH Terms
State-dependent alterations in sleep/wake architecture elicited by the M4 PAM VU0467154 - Relation to antipsychotic-like drug effects.
Gould RW, Nedelcovych MT, Gong X, Tsai E, Bubser M, Bridges TM, Wood MR, Duggan ME, Brandon NJ, Dunlop J, Wood MW, Ivarsson M, Noetzel MJ, Daniels JS, Niswender CM, Lindsley CW, Conn PJ, Jones CK
(2016) Neuropharmacology 102: 244-53
MeSH Terms: Allosteric Regulation, Animals, Arousal, Electroencephalography, Male, Polysomnography, Pyridazines, Rats, Receptor, Muscarinic M4, Sleep, Thiophenes
Added February 18, 2016
0 Communities
3 Members
0 Resources
11 MeSH Terms
Allosteric activation of M4 muscarinic receptors improve behavioral and physiological alterations in early symptomatic YAC128 mice.
Pancani T, Foster DJ, Moehle MS, Bichell TJ, Bradley E, Bridges TM, Klar R, Poslusney M, Rook JM, Daniels JS, Niswender CM, Jones CK, Wood MR, Bowman AB, Lindsley CW, Xiang Z, Conn PJ
(2015) Proc Natl Acad Sci U S A 112: 14078-83
MeSH Terms: Allosteric Regulation, Animals, Brain, Fluorescence, Glutamic Acid, Huntington Disease, Immunohistochemistry, Mice, Mice, Mutant Strains, Pyridazines, Receptor, Muscarinic M4, Rotarod Performance Test, Synaptic Transmission, Thiophenes
Added February 15, 2016
0 Communities
5 Members
0 Resources
14 MeSH Terms
TISSUE REGENERATION. Inhibition of the prostaglandin-degrading enzyme 15-PGDH potentiates tissue regeneration.
Zhang Y, Desai A, Yang SY, Bae KB, Antczak MI, Fink SP, Tiwari S, Willis JE, Williams NS, Dawson DM, Wald D, Chen WD, Wang Z, Kasturi L, Larusch GA, He L, Cominelli F, Di Martino L, Djuric Z, Milne GL, Chance M, Sanabria J, Dealwis C, Mikkola D, Naidoo J, Wei S, Tai HH, Gerson SL, Ready JM, Posner B, Willson JK, Markowitz SD
(2015) Science 348: aaa2340
MeSH Terms: Animals, Bone Marrow Transplantation, Colitis, Dinoprostone, Enzyme Inhibitors, Hematopoiesis, Hydroxyprostaglandin Dehydrogenases, Liver Regeneration, Mice, Mice, Knockout, Prostaglandins, Pyridines, Regeneration, Thiophenes
Added March 10, 2016
1 Communities
0 Members
0 Resources
14 MeSH Terms
RNA-seq identifies a role for the PPARβ/δ inverse agonist GSK0660 in the regulation of TNFα-induced cytokine signaling in retinal endothelial cells.
Savage SR, McCollum GW, Yang R, Penn JS
(2015) Mol Vis 21: 568-76
MeSH Terms: Cells, Cultured, Chemokine CCL8, Cytokines, Endothelial Cells, Gene Expression Regulation, Humans, PPAR delta, PPAR-beta, Retinal Vessels, Sequence Analysis, RNA, Signal Transduction, Sulfones, Thiophenes, Tumor Necrosis Factor-alpha
Added April 10, 2019
0 Communities
1 Members
0 Resources
MeSH Terms
An in vivo chemical genetic screen identifies phosphodiesterase 4 as a pharmacological target for hedgehog signaling inhibition.
Williams CH, Hempel JE, Hao J, Frist AY, Williams MM, Fleming JT, Sulikowski GA, Cooper MK, Chiang C, Hong CC
(2015) Cell Rep 11: 43-50
MeSH Terms: Animals, Cyclic AMP-Dependent Protein Kinases, Cyclic Nucleotide Phosphodiesterases, Type 4, Hedgehog Proteins, Phosphodiesterase 4 Inhibitors, Pyrimidinones, Receptors, G-Protein-Coupled, Signal Transduction, Small Molecule Libraries, Smoothened Receptor, Thiophenes, Transcriptional Activation, Zebrafish, Zebrafish Proteins
Added April 5, 2015
1 Communities
3 Members
0 Resources
14 MeSH Terms
Modulation of VEGF-induced retinal vascular permeability by peroxisome proliferator-activated receptor-β/δ.
Suarez S, McCollum GW, Bretz CA, Yang R, Capozzi ME, Penn JS
(2014) Invest Ophthalmol Vis Sci 55: 8232-40
MeSH Terms: Analysis of Variance, Animals, Capillary Permeability, Cell Membrane, Cells, Cultured, Claudin-1, Claudin-5, Electric Impedance, Endothelial Cells, Extracellular Signal-Regulated MAP Kinases, Humans, Immunohistochemistry, MAP Kinase Signaling System, Mice, Mice, Inbred C57BL, Models, Animal, Peroxisome Proliferator-Activated Receptors, Receptors, Vascular Endothelial Growth Factor, Retina, Retinal Vessels, Sulfones, Thiophenes, Vascular Endothelial Growth Factor A
Added February 19, 2015
1 Communities
1 Members
0 Resources
23 MeSH Terms
Selective activation of M4 muscarinic acetylcholine receptors reverses MK-801-induced behavioral impairments and enhances associative learning in rodents.
Bubser M, Bridges TM, Dencker D, Gould RW, Grannan M, Noetzel MJ, Lamsal A, Niswender CM, Daniels JS, Poslusney MS, Melancon BJ, Tarr JC, Byers FW, Wess J, Duggan ME, Dunlop J, Wood MW, Brandon NJ, Wood MR, Lindsley CW, Conn PJ, Jones CK
(2014) ACS Chem Neurosci 5: 920-42
MeSH Terms: Amphetamines, Animals, Association Learning, Brain, Cell Line, Central Nervous System Stimulants, Cholinergic Agents, Cricetulus, Dizocilpine Maleate, Dogs, Dose-Response Relationship, Drug, Excitatory Amino Acid Antagonists, Humans, Macaca fascicularis, Male, Mice, Inbred C57BL, Mice, Knockout, Motor Activity, Psychotropic Drugs, Pyridazines, Rats, Rats, Sprague-Dawley, Receptor, Muscarinic M4, Thiophenes
Added February 19, 2015
0 Communities
3 Members
0 Resources
24 MeSH Terms
Glucotoxicity targets hepatic glucokinase in Zucker diabetic fatty rats, a model of type 2 diabetes associated with obesity.
Ueta K, O'Brien TP, McCoy GA, Kim K, Healey EC, Farmer TD, Donahue EP, Condren AB, Printz RL, Shiota M
(2014) Am J Physiol Endocrinol Metab 306: E1225-38
MeSH Terms: Animals, Body Weight, Canagliflozin, Diabetes Mellitus, Type 2, Eating, Glucagon, Glucokinase, Glucose, Glucose Clamp Technique, Glucosides, Hyperglycemia, Hyperinsulinism, Immunohistochemistry, Liver, Male, Obesity, Organ Size, Oxygen Consumption, RNA, Messenger, Rats, Rats, Zucker, Sodium-Glucose Transporter 2, Sodium-Glucose Transporter 2 Inhibitors, Thiophenes
Added February 19, 2015
0 Communities
1 Members
0 Resources
24 MeSH Terms
A small-molecule benzimidazole derivative that potently activates AMPK to increase glucose transport in skeletal muscle: comparison with effects of contraction and other AMPK activators.
Lai YC, Kviklyte S, Vertommen D, Lantier L, Foretz M, Viollet B, Hallén S, Rider MH
(2014) Biochem J 460: 363-75
MeSH Terms: AMP-Activated Protein Kinases, Acetyl-CoA Carboxylase, Aminoimidazole Carboxamide, Animals, Benzimidazoles, Biphenyl Compounds, Enzyme Activation, Fatty Acids, Glucose, Glycogen, Male, Mice, Muscle Contraction, Muscle, Skeletal, Pyrones, Rats, Ribonucleotides, Thiophenes
Added August 18, 2014
0 Communities
1 Members
0 Resources
18 MeSH Terms