Results 71 to 80 of about 107,657 (326)
Journal of Medicinal Chemistry, 2019 The design, optimization, and evaluation of a series of novel imidazopyridazine-based subtype-selective positive allosteric modulators (PAMs) for the GABAA ligand-gated ion channel are described.
R. M. Owen +21 more
semanticscholar +1 more source
Positive allosteric modulation of a GPCR ternary complex
Science AdvancesAbstract The activation of a G protein-coupled receptor (GPCR) leads to the formation of a ternary complex between agonist, receptor, and G protein that is characterised by high-affinity binding. Allosteric modulators bind to a distinct binding site from the orthosteric agonist and can modulate both the affinity and ...
Wessel A. C. Burger +4 more
openaire +2 more sources
The therapeutic promise of positive allosteric modulation of nicotinic receptors [PDF]
European Journal of Pharmacology, 2014 In the central nervous system, deficits in cholinergic neurotransmission correlate with decreased attention and cognitive impairment, while stimulation of neuronal nicotinic acetylcholine receptors improves attention, cognitive performance and neuronal resistance to injury as well as produces robust analgesic and anti-inflammatory effects. The rational
openaire +2 more sources
British Journal of Pharmacology, 2019 The δ‐opioid receptor is an emerging target for the management of chronic pain and depression. Biased signalling, the preferential activation of one signalling pathway over another downstream of δ‐receptors, may generate better therapeutic profiles.
M. Stanczyk +5 more
semanticscholar +1 more source
Effect of γ value on binding of allosteric modulator to two allosteric sites.
, 2019 Simulation of tracer binding (ordinate) in the presence an allosteric modulator binding to two allosteric sites for various combinations of positive and negative cooperativity with the tracer indicated at headings of individual plots.
Esam E. El-Fakahany (339452) +3 more
core +1 more source
Effect of δ value on binding of allosteric modulator to two allosteric sites.
, 2019 Simulation of tracer binding (ordinate) in the presence an allosteric modulator binding to two allosteric sites for various combinations of positive and negative cooperativity with the tracer indicated at headings of individual plots.
Esam E. El-Fakahany (339452) +3 more
core +1 more source
FEBS Letters, EarlyView.Biomolecular condensates formed by fused in sarcoma (FUS) are dissolved by high ATP concentrations yet persist in cells. Using a reconstituted system, we demonstrate that valosin‐containing protein (VCP), an AAA+ ATPase, counteracts ATP‐driven dissolution of FUS condensates through its D2 ATPase activity.
Hitomi Kimura +2 more
wiley +1 more source
Concentration dependence of binding of allosteric modulator to two allosteric sites.
, 2019 Simulation of tracer binding (ordinate) in the presence an allosteric modulator binding to two allosteric sites for various combinations of positive and negative cooperativity with the tracer indicated at headings of individual plots.
Esam E. El-Fakahany (339452) +3 more
core +1 more source
pH‐mediated activation of the lysosomal arginine sensor SLC38A9
FEBS Letters, EarlyView.Cells monitor nutrient levels via the lysosomal transporter SLC38A9 to activate the mechanistic target of rapamycin complex 1 (mTORC1). This study reveals that SLC38A9 function is regulated by pH. We identified histidine 544 as a critical pH sensor that undergoes conformational changes to control amino acid efflux from lysosomes; therefore, it ...
Xuelang Mu, Ampon Sae Her, Tamir Gonen
wiley +1 more source
Development of pyrimidone D1 dopamine receptor positive allosteric modulators
Bioorganic & Medicinal Chemistry Letters, 2021 MLS1082 is a structurally novel pyrimidone-based D1-like dopamine receptor positive allosteric modulator. Potentiation of D1 dopamine receptor (D1R) signaling is a therapeutic strategy for treating neurocognitive disorders. Here, we investigate the relationship between D1R potentiation and two prominent structural features of MLS1082, namely the ...
Kathryn D, Luderman +6 more
openaire +3 more sources