Results 61 to 70 of about 11,411 (182)

Mechanistic insights into the versatile stoichiometry and biased signaling of the apelin receptor-arrestin complex

Nature Communications
The apelin receptor (APJR) plays a pivotal role in regulating cardiovascular and metabolic health1,2. Understanding the mechanisms of biased agonism at APJR is crucial for drug discovery, as stimulation of the β-arrestin pathway may lead to some adverse ...
Yang Yue, Chanjuan Xu, Lijie Wu, Man Na, Kexin Xu, Xuan Chen, Yuxuan Song, Sichun Weng, Lu Xu, Fei Li, Xi Lin, Arthur Wang, Jianfeng Liu, Fei Xu   +13 more
doaj   +1 more source

β-Arrestin-biased Agonism at the β2-Adrenergic Receptor [PDF]

Journal of Biological Chemistry, 2008
Classically, the beta 2-adrenergic receptor (beta 2AR) and other members of the seven-transmembrane receptor (7TMR) superfamily activate G protein-dependent signaling pathways in response to ligand stimulus. It has recently been discovered, however, that a number of 7TMRs, including beta 2AR, can signal via beta-arrestin-dependent pathways independent ...
Matthew T, Drake, Jonathan D, Violin, Erin J, Whalen, James W, Wisler, Sudha K, Shenoy, Robert J, Lefkowitz   +5 more
openaire   +2 more sources

Signal transduction mechanism of biased ligands at histamine H2 receptors [PDF]

, 2014
7TMRs (seven-transmembrane receptors) exist as conformational collections in which different conformations would lead to differential downstream behaviours such as receptor phosphorylation, G-protein activation and receptor internalization.
Alonso, Natalia, Davio, Carlos Alberto, Echeverría, Emiliana Beatriz, Fernández, Natalia Brenda, Monczor, Federico, Shayo, Carina Claudia   +5 more
core   +1 more source

Biased agonism: An emerging paradigm in GPCR drug discovery [PDF]

Bioorganic & Medicinal Chemistry Letters, 2016
G protein coupled receptors have historically been one of the most druggable classes of cellular proteins. The members of this large receptor gene family couple to primary effectors, G proteins, that have built in mechanisms for regeneration and amplification of signaling with each engagement of receptor and ligand, a kinetic event in itself. In recent
Zoran, Rankovic, Tarsis F, Brust, Laura M, Bohn   +2 more
openaire   +2 more sources

Functional divergence in the role of N-linked glycosylation in smoothened signaling [PDF]

, 2015
The G protein-coupled receptor (GPCR) Smoothened (Smo) is the requisite signal transducer of the evolutionarily conserved Hedgehog (Hh) pathway. Although aspects of Smo signaling are conserved from Drosophila to vertebrates, significant differences have ...
A Helenius, A Ruiz i Altaba, AG Soto, AG Soto, AH Polizio, AH Polizio, AJ Petrescu, AJ Zhu, AM Wilbanks, Angela M. Arensdorf, Ashley Truong, B Sivertsen, BJ Arey, BR Myers, C Torroja, C Wang, C Wang, CE Carroll, D Maier, D Nedelcu, D Rendie, D Shi, Daniel P. Stewart, David J. Robbins, DJ Casso, DJ Robbins, DM Stone, Edgar Angelats, F Landomiel, F Shen, G Navarro, Gemma Navarro, H Sasaki, J Alcedo, J Bischof, J Briscoe, J He, J Taipale, J Taipale, JD Violin, JJ Kovacs, JK Chen, JK Chen, Joseph T. Opferman, JP Incardona, KC Corbit, L Zhou, LW McGinnes, M Murone, M van den Heuvel, M Wheatley, MF Tansky, MT Barakat, N Denef, NA Riobo, Peter J. McCormick, PM Lanctot, PW Ingham, R Rana, R Rohatgi, R Rohatgi, R Schroder, R Schroder, R Teperino, R Xia, Rajat Rohatgi, RT Strachan, S Li, S Marada, S Mukhopadhyay, S Nachtergaele, S Nachtergaele, S Rajagopal, S Yao, Sigrid Nachtergaele, SK Ogden, Stacey K. Ogden, Suresh Marada, T Von Ohlen, V Marigo, X Lu, Y Nakano, Y Zhao, YH Belgacem   +83 more
core   +3 more sources

Mitragynine/Corynantheidine Pseudoindoxyls As Opioid Analgesics with Mu Agonism and Delta Antagonism, Which Do Not Recruit beta-Arrestin-2. [PDF]

, 2016
Natural products found in Mitragyna speciosa, commonly known as kratom, represent diverse scaffolds (indole, indolenine, and spiro pseudoindoxyl) with opioid activity, providing opportunities to better understand opioid pharmacology.
Borics, Attila, Marrone, Gina F., Narayan, Ankita, Palmer, Travis C., Szabó, Márton Richárd, Váradi, András   +5 more
core   +1 more source

G protein-coupled receptor-biased signaling: potential drug discovery to facilitate treatment of metabolic diseases

Acta Materia Medica
G protein-coupled receptors (GPCRs) are important, potential drug targets for the treatment of metabolic disorders, such as obesity. GPCRs crosstalk with several transducers, including heterotrimeric G proteins, GPCR kinases (GRKs), and β-arrestins. GPCR-
Shengnan Shen, Qiwen Liao, Liwei Gu, Yongping Zhu, Yanqing Liu, Xinwei Zhang, Junzhe Zhang, Qiaoli Shi, Yuxiang Sun, Jigang Wang, Ligen Lin   +10 more
doaj   +1 more source

Advances in Achieving Opioid Analgesia Without Side Effects

Frontiers in Pharmacology, 2018
Opioids are the most effective drugs for the treatment of severe pain, but they also cause addiction and overdose deaths, which have led to a worldwide opioid crisis. Therefore, the development of safer opioids is urgently needed.
Halina Machelska, Melih Ö. Celik
doaj   +1 more source

Evaluation of Biased and Balanced Salvinorin A Analogs in Preclinical Models of Pain

Frontiers in Neuroscience, 2020
In the search for safer, non-addictive analgesics, kappa opioid receptor (KOPr) agonists are a potential target, as unlike mu-opioid analgesics, they do not have abuse potential.
Kelly F. Paton, Andrew Biggerstaff, Sophia Kaska, Rachel S. Crowley, Anne C. La Flamme, Anne C. La Flamme, Thomas E. Prisinzano, Thomas E. Prisinzano, Bronwyn M. Kivell   +8 more
doaj   +1 more source

A GLP-1 analogue optimized for cAMP-biased signaling improves weight loss in obese mice

Molecular Metabolism
Objective: Glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) agonism is foundational to modern obesity pharmacotherapies. These compounds were engineered for maximal G protein alpha(s) (Gsα) signaling potency and downstream cAMP production. However, this
Jonathan D. Douros, Aaron Novikoff, Barent DuBois, Rebecca Rohlfs, Jacek Mokrosinski, Wouter F.J. Hogendorf, Robert Augustin, Myrte Merkestein, Lene Brandt Egaa Martini, Lars Linderoth, Elliot Gerrard, Janos Tibor Kodra, Jenny Norlin, Nikolaj Kulahin Roed, Anouk Oldenburger, Stephanie A. Mowery, Maria Waldhoer, Diego Perez-Tilve, Brian Finan, Steffen Reedtz-Runge, Timo D. Müller, Patrick J. Knerr   +21 more
doaj   +1 more source