Results 21 to 30 of about 31,985 (308)

The unconventional activation of the muscarinic acetylcholine receptor M4R by diverse ligands

Nature Communications, 2022
The authors report the structural characterization of M4R selective allosteric agonist, compound-110, as well as agonist iperoxo and positive allosteric modulator LY2119620.
Jingjing Wang, Meng Wu, Zhangcheng Chen, Lijie Wu, Tian Wang, Dongmei Cao, Huan Wang, Shenhui Liu, Yueming Xu, Fei Li, Junlin Liu, Na Chen, Suwen Zhao, Jianjun Cheng, Sheng Wang, Tian Hua   +15 more
doaj   +1 more source

Allosterism vs. Orthosterism: Recent Findings and Future Perspectives on A2B AR Physio-Pathological Implications

Frontiers in Pharmacology, 2021
The development of GPCR (G-coupled protein receptor) allosteric modulators has attracted increasing interest in the last decades. The use of allosteric modulators in therapy offers several advantages with respect to orthosteric ones, as they can fine ...
Elisabetta Barresi, Claudia Martini, Federico Da Settimo, Giovanni Greco, Sabrina Taliani, Chiara Giacomelli, Maria Letizia Trincavelli   +6 more
doaj   +1 more source

Bitopic binding mode of an M1 muscarinic acetylcholine receptor agonist associated with adverse clinical trial outcomes [PDF]

, 2018
The realisation of the therapeutic potential of targeting the M1 muscarinic acetylcholine receptor (M1 mAChR) for the treatment of cognitive decline in Alzheimer's disease has prompted the discovery of M1 mAChR ligands showing efficacy in alleviating ...
Bradley, Sophie J., Broad, Lisa M., Brooke, Simon M., Bundgaard, Christoffer, Christopoulos, Arthur, Crabtree, Michael D., Dwomoh, Louis, Felder, Christian C., Langmead, Christopher J., Mogg, Adrian J., Molloy, Colin, Sanger, Helen E., Sexton, Patrick M., Thompson, Karen J., Tobin, Andrew B.   +14 more
core   +1 more source

Allosteric modulators enhance agonist efficacy by increasing the residence time of a GPCR in the active state

Nature Communications, 2021
Here, the authors use smFRET to assess the structural dynamics of metabotropic glutamate receptor mGlu2 and show that a positive allosteric modulator or the Gi protein stabilize mGlu2 in the glutamate-induced active state, leading to the full activation ...
Anne-Marinette Cao, Robert B. Quast, Fataneh Fatemi, Philippe Rondard, Jean-Philippe Pin, Emmanuel Margeat   +5 more
doaj   +1 more source

Heterobiaryl and heterobiaryl ether derived M5 positive allosteric modulators [PDF]

Bioorganic & Medicinal Chemistry Letters, 2010
This Letter describes a chemical lead optimization campaign directed at VU0238429, the first M(5)-preferring positive allosteric modulator (PAM), discovered through analog work around VU0119498, a pan G(q) mAChR M(1), M(3), M(5) PAM. An iterative parallel synthesis approach was employed to incorporate basic heterocycles to improve physiochemical ...
Thomas M, Bridges, J Phillip, Kennedy, Corey R, Hopkins, P Jeffrey, Conn, Craig W, Lindsley   +4 more
openaire   +2 more sources

The therapeutic potential of allosteric ligands for free fatty acid sensitive GPCRs [PDF]

, 2013
G protein coupled receptors (GPCRs) are the most historically successful therapeutic targets. Despite this success there are many important aspects of GPCR pharmacology and function that have yet to be exploited to their full therapeutic potential.
Hudson, Brian D., Milligan, Graeme, Ulven, Trond   +2 more
core   +1 more source

GABAA receptor: Positive and negative allosteric modulators [PDF]

Neuropharmacology, 2018
gamma-Aminobutyric acid (GABA)-mediated inhibitory neurotransmission and the gene products involved were discovered during the mid-twentieth century. Historically, myriad existing nervous system drugs act as positive and negative allosteric modulators of these proteins, making GABA a major component of modern neuropharmacology, and suggesting that many
openaire   +2 more sources

LY404187: A Novel Positive Allosteric Modulator of AMPA Receptors [PDF]

CNS Drug Reviews, 2002
ABSTRACTLY404187 is a selective, potent and centrally active positive allosteric modulator of AMPA receptors. LY404187 preferentially acts at recombinant human homomeric GluR2 and GluR4 versus GluR1 and GluR3 AMPA receptors. In addition, LY404187 potentiates the flip splice variant of these AMPA receptors to a greater degree than the flop splice ...
Jennifer C, Quirk, Eric S, Nisenbaum
openaire   +2 more sources

Three classes of ligands each bind to distinct sites on the orphan G protein-coupled receptor GPR84 [PDF]

, 2017
Medium chain fatty acids can activate the pro-inflammatory receptor GPR84 but so also can molecules related to 3,3′-diindolylmethane. 3,3′-Diindolylmethane and decanoic acid acted as strong positive allosteric modulators of the function of each other and
De Vos, Steve, Gosmini, Romain, Hudson, Brian D., Jenkins, Laura, Labéguère, Frédéric, Mahmud, Zobaer Al, Milligan, Graeme, Tikhonova, Irina G., Ulven, Trond   +8 more
core   +3 more sources

Contrasting properties of α7-selective orthosteric and allosteric agonists examined on native nicotinic acetylcholine receptors. [PDF]

PLoS ONE, 2013
Subtype-selective ligands are important tools for the pharmacological characterisation of neurotransmitter receptors. This is particularly the case for nicotinic acetylcholine receptors (nAChRs), given the heterogeneity of their subunit composition.
JasKiran K Gill, Anna Chatzidaki, Daniel Ursu, Emanuele Sher, Neil S Millar   +4 more
doaj   +1 more source