Results 121 to 130 of about 31,985 (308)

Synthesis and pharmacological profiling of analogues of benzyl quinolone carboxylic acid (BQCA) as allosteric modulators of the M1 muscarinic receptor [PDF]

, 2013
Established therapy in Alzheimer’s disease involves potentiation of the endogenous orthosteric ligand, acetylcholine, at the M1 muscarinic receptors found in higher concentrations in the cortex and hippocampus.
Arthur Christopoulos, Aurelio L., Avlani V. A., Barbosa J., Bell R. P., Ben Capuano, Bunce R. A., Canals M., Cao X., Casara P., Celine Valant, Conn P. J., Decker M., Eaton P. E., Gould R. G., Holden M., Koguro K., Kuduk S. D., Kuduk S. D., Kuduk S. D., Kuduk S. D., Kuduk S. D., Kuduk S. D., Kuduk S. D., Kuduk S. D., Langmead C. J., Lauer W. M., Leach K., Ma L., Maffioli S. I., Meanwell N. A., Medeiros R. R., Patrick M. Sexton, Peter J. Scammells, Podányi B., Reid P. R., Shailesh N. Mistry, Shirey J. K., Wess J., Wise W. M., Yang F. V., Zewge D., Zhang Y., Škugor M. M.   +43 more
core   +2 more sources

TRIM40 Drives Pathological Cardiac Hypertrophy and Heart Failure via Ubiquitination of PKN2

Advanced Science, EarlyView.
This study identifies the E3 ligase TRIM40 as a key driver of pathological cardiac hypertrophy. TRIM40 binds PKN2 via its B‐box domain and, through its C29‐dependent catalytic activity, mediates K63‐linked ubiquitination of PKN2. This modification enhances PKN2 phosphorylation at Ser815, thereby driving hypertrophy.
Risheng Zhao, Xiaoli Cui, Huizhu Du, Zhuoqun Wang, Chang Liu, Linxin Zhang, Jianing Qi, Di Yang, Hui Yu, Shuang Yan, Wei Liu, Haiming Sun, Mengyang Wang   +12 more
wiley   +1 more source

T‐495, a novel low cooperative M1 receptor positive allosteric modulator, improves memory deficits associated with cholinergic dysfunction and is characterized by low gastrointestinal side effect risk

Pharmacology Research & Perspectives, 2020
M1 muscarinic acetylcholine receptor (M1R) activation can be a new therapeutic approach for the treatment of cognitive deficits associated with cholinergic hypofunction. However, M1R activation causes gastrointestinal (GI) side effects in animals.
Takao Mandai, Yuu Sako, Emi Kurimoto, Yuji Shimizu, Minoru Nakamura, Makoto Fushimi, Ryouta Maeda, Maki Miyamoto, Haruhide Kimura   +8 more
doaj   +1 more source

Allosteric Inhibition of Factor XIIIa. Non-Saccharide Glycosaminoglycan Mimetics, but Not Glycosaminoglycans, Exhibit Promising Inhibition Profile [PDF]

, 2016
Factor XIIIa (FXIIIa) is a transglutaminase that catalyzes the last step in the coagulation process. Orthostery is the only approach that has been exploited to design FXIIIa inhibitors.
Afosa, Daniel K., Al-Horani, Rami A., Desai, Umesh R., Karuturi, Rajesh, Lee, Michael   +4 more
core   +4 more sources

Automatically Defining Protein Words for Diverse Functional Predictions Based on Attention Analysis of a Protein Language Model

Advanced Science, EarlyView.
Understanding protein sequence–function relationships remains challenging due to poorly defined motifs and limited residue‐level annotations. An annotation‐agnostic framework is introduced that segments protein sequences into “protein words” using attention patterns from protein language models.
Hedi Chen, Jingrui Zhong, Xiaochun Zhang, Jingke Chen, Lin Guo, Xiaoliang Xiong, Xiaonan Zhang, Xiangyu Liu, Bailong Xiao, Boxue Tian   +9 more
wiley   +1 more source

Sex-dependent anti-stress effect of an α5 subunit containing GABAA receptor positive allosteric modulator

Frontiers in Pharmacology, 2016
Rationale: Current first-line treatments for stress-related disorders such as Major Depressive Disorder (MDD) act on monoaminergic systems and take weeks to achieve a therapeutic effect with poor response and low remission rates.
Sean C. Piantadosi, Sean C. Piantadosi, Beverly J French, Michael M Poe, Tamara Timić, Bojan Marković, Mohan Pabba, Marianne Seney, Hyunjung Oh, Beverley Anne Orser, Miroslav M Savic, James M Cook, Etienne Sibille, Etienne Sibille, Etienne Sibille, Etienne Sibille   +15 more
doaj   +1 more source

Novel fused arylpyrimidinone based allosteric modulators of the M1 muscarinic acetylcholine receptor [PDF]

, 2016
Benzoquinazolinone 1 is a positive allosteric modulator (PAM) of the M1 muscarinic acetylcholine receptor (mAChR), which is significantly more potent than the prototypical PAM, 1-(4-methoxybenzyl)-4-oxo-1,4-dihydroquinoline- 3-carboxylic acid (BQCA). In
Capuano, Ben, Christopoulos, Arthur, Jörg, Manuela, Lane, J Robert, Lane, J. Robert, Lim, Herman, Mistry, Shailesh N, Scammells, Peter J, Scammells, Peter J.   +8 more
core   +2 more sources

Lipid Pocket Binders Impose Allosteric Changes of Protein Dynamics Around the Active Site of the Protein Kinase p38α

Angewandte Chemie International Edition, EarlyView.
Used in search of novel allosteric sites in the serine/threonine kinase p38α, NMR spectroscopy reveals a dynamic coupling between the catalytic and lipid pockets. The findings uncover a motional interdependence that links distant regions of the enzyme, highlighting the lipid pocket as a promising site for allosteric intervention.
Sara Medina Gómez, Laurin T. Homberg, Mike Bührmann, Daniel Rauh, Rasmus Linser   +4 more
wiley   +1 more source

mGluR2-Positive Allosteric Modulators: Therapeutic Potential for Treating Cocaine Abuse? [PDF]

Neuropsychopharmacology, 2010
The heterogeneous distribution of the metabotropic glutamate receptors (mGluRs) in the mammalian brain and the variety of receptor subtypes potentially regulating a range of neuropharmacological activities have long been attractive targets for the development of compounds that selectively interact with the eight identified receptor subtypes.
openaire   +2 more sources

Selective modulators of α5-containing GABAA receptors and their therapeutic significance [PDF]

, 2015
GABA receptors containing the α subunit (αGABARs) are found mainly in the hippocampus where they mediate a tonic chloride leak current and contribute a slow component to GABAergic inhibitory synaptic currents.
Lynch, Joseph W., Soh, Ming Shiuan
core   +1 more source