23 papers · ranked by Valyu relevance
James P. Higham, David Colquhoun
A fundamental mistake in receptor theory has led to an enduring misunderstanding of how to estimate the affinity and efficacy of an agonist. These properties are inextricably linked and cannot be easily separated in any case where the binding of a ligand induces a conformation change in its receptor. Consequently…
Rustin R. Lovewell, Solomon Langermann, Dallas B. Flies
The immune system maintains the health of an organism through complex sensing and communication mechanisms. Receptors on the surface of immune cells respond to stimuli resulting in activity described at its most basic as inhibitory or stimulatory. Significant progress in therapeutic intervention has occurred by…
Wolfgang Sadee, Mariana Spetea
G-protein-coupled receptors (GPCRs) are ubiquitous sensors and regulators of cellular functions. Each GPCR exists in complex aggregates with multiple resting and active conformations. Designed to detect weak stimuli, GPCRs can also activate spontaneously, resulting in basal ligand-free signaling. Agonists trigger a…
Harry Ridgway, Graham J. Moore, Laura Kate Gadanec, John M. Matsoukas + 4 more
'John M. Matsoukas' 'Mohsin Saleet Jafri' 'Carola Yvette Förster' 'Tarun W. Dasari' 'David Puett'] Recent bioassay studies have unexpectedly supported the high (computationally predicted) binding affinities of angiotensin receptor blockers (ARBs) at α-adrenergic receptors (αARs) in isolated smooth muscle. Computational…
Michael J. Robertson, Makaía M. Papasergi-Scott, Maria Claudia Peroto, Balazs R. Varga + 2 more
Distinct ligands for the same G-protein coupled receptor (GPCR) activate intracellular signaling partners to varying extents, but the molecular mechanisms driving these differences remains elusive. Hypothesizing that such differences in signaling efficacy may be captured structurally in intermediate states under…
Friederike Wunsch, Michael Kauk, Jenny Filor, Gerhard Wolber + 3 more
For the prototypic M_2_ receptor it has been previously demonstrated that dualsteric partial agonists can stabilize both, active and inactive receptor states, but it remains unclear whether orthosteric partial agonists have a similar mechanism. Here, we apply dynamic pharmacophores to unveil binding mode ensembles for…
Stephen P. H. Alexander, Arthur Christopoulos, Anthony P. Davenport, Eamonn Kelly + 162 more
The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is an emphasis on selective…
V. Şorodoc, G. Rusu-Zota, P. Nechita, C. Moraru + 1 more
Agmatine (AG), idazoxan (IDZ), and efaroxan (EFR) are imidazoline receptor ligands with beneficial effects in central nervous system disorders. The present study aimed to evaluate the interaction between AG, IDZ, and EFR with an opiate, tramadol (TR), in a conditioned place preference (CPP) paradigm. In the experiment…
Laura Ferrante, Anna Boesendorfer, Benedikt Baumgartner, Manuel Catalano + 3 more
Following limb amputation and targeted muscle reinnervation (TMR), nerves supplying agonist and antagonist muscles are rerouted into separate targeted muscles, disrupting natural neuromechanical coupling between muscle groups. Using high-density intramuscular microelectrode arrays in reinnervated muscles, we show that…
Taylor L. Mighell, Ben Lehner
G-protein coupled receptors (GPCRs) are the most abundant class of human receptors and drug targets. The vast majority of GPCR drugs bind the conserved orthosteric pocket, which can lead to non-specificity and toxicity. Precision modalities such as biased signaling and allosteric modulation could lead to GPCR…
Won Kyu Kim, Kiri Choi, Changbong Hyeon, Seogjoo Jang
Department of Chemistry and Biochemistry, Queens College, City University of New York, 65-30 Kissena Boulevard, Queens, NY 11367 & PhD programs in Chemistry and Physics, Graduate Center, City University of New York, NY 10016 and Korea Institute for Advanced Study, Hoegiro 85, Dongdaemun-gu, Seoul 02455, Korea (Dated…
Authors not listed
Targeting retinoic acid-related orphan receptor γ (RORγ) with inverse agonists presents a promising therapeutic strategy for treating autoimmune diseases, including psoriasis, rheumatoid arthritis, and multiple sclerosis. Through structure-based virtual screening, we identified a lupane-type pentacyclic triterpenoid…
Sabine Willems, Romy Busch, Felix Nawa, Marco Ballarotto + 12 more
Nuclear receptor related 1 (Nurr1, NR4A2) is a ligand-sensing transcription factor with neuroprotective and anti-inflammatory roles widely distributed in the CNS. Pharmacological Nurr1 modulation is considered a promising experimental strategy in Parkinson's and Alzheimer's disease but target validation is incomplete.…
Stephen P. H. Alexander, Anthony P. Davenport, Eamonn Kelly, Alasdair J. Gibb + 203 more
The Concise Guide to Pharmacology 2025/26 marks the seventh edition in this series of biennial publications in the British Journal of Pharmacology. Presented in landscape format, the guide provides a comparative overview of the pharmacology of drug target families. The concise nature of the Concise Guide refers to the…
Authors not listed
GPR3 belongs to the protein superfamily of G protein-coupled receptors (GPCRs) and plays a central role in both benign and malignant physiological processes, such as energy expenditure in adipocytes and Alzheimer’s disease pathology, respectively. Despite the therapeutic potential of both receptor agonists and inverse…
Zach Walsh, Ozden Merve Mollaahmetoglu, Joseph Rootman, Shannon Golsof + 4 more
'Shannon Golsof' 'Johanna Keeler' 'Beth Marsh' 'David J. Nutt' 'Celia J. A. Morgan'] In the original publication,1 an error was made in the introduction. In the first sentence of the Background section, ‘agonist’ should have been ‘antagonist’. This has now been corrected in both the online PDF and HTML versions of this…
Xiaohan Zhou, Maria Shemeteva, Louis-Phillipe Picard, François Simon + 5 more
Many G protein coupled receptors (GPCRs) exhibit constitutive (basal) activity, where they can signal in the absence of ligand binding through spontaneous conformational transitions that facilitate G protein coupling and downstream signaling. This intrinsic baseline activity is critical for cellular homeostasis and can…
Philipp Maurus, Daniel P. Armstrong, Stephen H. Scott, Tyler Cluff
task-dependent feedback control Authors: ['Philipp Maurus' 'Daniel P. Armstrong' 'Stephen H. Scott' 'Tyler Cluff'] Humans and other animals coactivate agonist and antagonist muscles in many motor actions. Increases in muscle coactivation are thought to leverage viscoelastic properties of skeletal muscles to provide…
Authors not listed
Allosteric modulators offers a promising approach for targeting receptor function in pathological contexts. Although numerous orthosteric ligands have been developed, the discovery of allosteric inhibitors remains limited, hindered by challenges with identifying modulators and the perceived lower druggability of…
Ali Y. Benkherouf
To my grandmother, whose belief in me remains unwavering, and to the cherished ones no longer with us. As stars pierce the night's veil, so has my family illuminated my path. This work stands in tribute to the trailblazers of this discipline, and to humanity's enduring spirit, always seeking nature's gentle touch.
Joshua D. Frenster, Hediye Erdjument-Bromage, Wenke Liu, Gabriele Stephan + 13 more
GPR133 (ADGRD1), an adhesion G protein-coupled receptor, supports growth of glioblastoma, a brain malignancy. We demonstrated that GPR133 is intramolecularly cleaved, and that dissociation of its N-terminal and C-terminal fragments (NTF and CTF) at the plasma membrane correlates with increased receptor signaling.…
Alice Valentini, Bethany Dibnah, Marija Ciba, Trond Ulven + 2 more
G protein coupled receptors (GPCRs) are the largest family of signalling proteins and highly successful drug targets. To date, most GPCR drugs interact with the binding pocket for the natural ligand, typically near the extracellular part of the transmembrane region. Recent advancements in structural biology have…
Spencer Kim, Dylan Gray, Michelle Shanguhyia, Rachel Steinhardt
Recreating the signaling profile a chemical synapse to analyze serotonin receptor activation is a challenge. This is due in part to the kinetics of the synapse, where neurotransmitters are rapidly released and quickly cleared by active reuptake machinery. One strategy to produce a rapid rise in a bio-orthogonally…