Search Results - "Sexton, M"

Allosteric modulation of G protein-coupled receptors: A pharmacological perspective by Keov, Peter, Sexton, Patrick M., Christopoulos, Arthur

“…G protein-coupled receptor (GPCR)-based drug discovery has traditionally focused on targeting the orthosteric site for the endogenous agonist. However, many…”
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A kinetic view of GPCR allostery and biased agonism by Lane, J Robert, May, Lauren T, Parton, Robert G, Sexton, Patrick M, Christopoulos, Arthur

“…Allosteric modulation and biased agonism at GPCRs could be manifestations of the same underlying 'conformational selection' mechanism, and these can be…”
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Phase-plate cryo-EM structure of a class B GPCR–G-protein complex by Liang, Yi-Lynn, Khoshouei, Maryam, Radjainia, Mazdak, Zhang, Yan, Glukhova, Alisa, Tarrasch, Jeffrey, Thal, David M., Furness, Sebastian G. B., Christopoulos, George, Coudrat, Thomas, Danev, Radostin, Baumeister, Wolfgang, Miller, Laurence J., Christopoulos, Arthur, Kobilka, Brian K., Wootten, Denise, Skiniotis, Georgios, Sexton, Patrick M.

“…Class B G-protein-coupled receptors are major targets for the treatment of chronic diseases, such as osteoporosis, diabetes and obesity. Here we report the…”
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G Protein-Coupled Receptors Targeting Insulin Resistance, Obesity, and Type 2 Diabetes Mellitus by Riddy, Darren M, Delerive, Philippe, Summers, Roger J, Sexton, Patrick M, Langmead, Christopher J

“…G protein-coupled receptors (GPCRs) continue to be important discovery targets for the treatment of type 2 diabetes mellitus (T2DM). Many GPCRs are directly…”
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Structure of the Adenosine A1 Receptor Reveals the Basis for Subtype Selectivity by Glukhova, Alisa, Thal, David M., Nguyen, Anh T., Vecchio, Elizabeth A., Jörg, Manuela, Scammells, Peter J., May, Lauren T., Sexton, Patrick M., Christopoulos, Arthur

“…The adenosine A1 receptor (A1-AR) is a G-protein-coupled receptor that plays a vital role in cardiac, renal, and neuronal processes but remains poorly targeted…”
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Phase-plate cryo-EM structure of a biased agonist-bound human GLP-1 receptor–Gs complex by Liang, Yi-Lynn, Khoshouei, Maryam, Glukhova, Alisa, Furness, Sebastian G. B., Zhao, Peishen, Clydesdale, Lachlan, Koole, Cassandra, Truong, Tin T., Thal, David M., Lei, Saifei, Radjainia, Mazdak, Danev, Radostin, Baumeister, Wolfgang, Wang, Ming-Wei, Miller, Laurence J., Christopoulos, Arthur, Sexton, Patrick M., Wootten, Denise

“…The structure of the glucagon-like peptide 1 receptor (GLP-1R) with its biased agonist exendin-P5 sheds light on both receptor activation and the mechanism of…”
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Activation and allosteric modulation of a muscarinic acetylcholine receptor by Kruse, Andrew C., Ring, Aaron M., Manglik, Aashish, Hu, Jianxin, Hu, Kelly, Eitel, Katrin, Hübner, Harald, Pardon, Els, Valant, Celine, Sexton, Patrick M., Christopoulos, Arthur, Felder, Christian C., Gmeiner, Peter, Steyaert, Jan, Weis, William I., Garcia, K. Christopher, Wess, Jürgen, Kobilka, Brian K.

“…Despite recent advances in crystallography and the availability of G-protein-coupled receptor (GPCR) structures, little is known about the mechanism of their…”
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Cryo-EM structure of the active, Gs-protein complexed, human CGRP receptor by Liang, Yi-Lynn, Khoshouei, Maryam, Deganutti, Giuseppe, Glukhova, Alisa, Koole, Cassandra, Peat, Thomas S., Radjainia, Mazdak, Plitzko, Jürgen M., Baumeister, Wolfgang, Miller, Laurence J., Hay, Deborah L., Christopoulos, Arthur, Reynolds, Christopher A., Wootten, Denise, Sexton, Patrick M.

“…Calcitonin gene-related peptide (CGRP) is a widely expressed neuropeptide that has a major role in sensory neurotransmission. The CGRP receptor is a…”
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Bridging the gap: bitopic ligands of G-protein-coupled receptors by Lane, J. Robert, Sexton, Patrick M, Christopoulos, Arthur

“…Although classical approaches to G-protein-coupled receptor (GPCR) drug design have targeted the orthosteric binding site, potentially all GPCRs possess…”
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Glucagon-Like Peptide-1 and Its Class B G Protein-Coupled Receptors: A Long March to Therapeutic Successes by Graaf, Chris de, Donnelly, Dan, Wootten, Denise, Lau, Jesper, Sexton, Patrick M, Miller, Laurence J, Ahn, Jung-Mo, Liao, Jiayu, Fletcher, Madeleine M, Yang, Dehua, Brown, Alastair J H, Zhou, Caihong, Deng, Jiejie, Wang, Ming-Wei

“…The glucagon-like peptide (GLP)-1 receptor (GLP-1R) is a class B G protein-coupled receptor (GPCR) that mediates the action of GLP-1, a peptide hormone…”
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Polar transmembrane interactions drive formation of ligand-specific and signal pathway-biased family B G protein-coupled receptor conformations by Wootten, Denise, Simms, John, Miller, Laurence J., Christopoulos, Arthur, Sexton, Patrick M.

“…Recently, the concept of ligand-directed signaling—the ability of different ligands of an individual receptor to promote distinct patterns of cellular…”
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Climate model errors, feedbacks and forcings: a comparison of perturbed physics and multi-model ensembles by Collins, Matthew, Booth, Ben B. B, Bhaskaran, B, Harris, Glen R, Murphy, James M, Sexton, David M. H, Webb, Mark J

“…Ensembles of climate model simulations are required for input into probabilistic assessments of the risk of future climate change in which uncertainties are…”
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Allostery and Biased Agonism at Class B G Protein-Coupled Receptors by Wootten, Denise, Miller, Laurence J, Koole, Cassandra, Christopoulos, Arthur, Sexton, Patrick M

“…Class B G protein-coupled receptors (GPCRs) respond to paracrine or endocrine peptide hormones involved in control of bone homeostasis, glucose regulation,…”
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Crystal structures of the M1 and M4 muscarinic acetylcholine receptors by Thal, David M., Sun, Bingfa, Feng, Dan, Nawaratne, Vindhya, Leach, Katie, Felder, Christian C., Bures, Mark G., Evans, David A., Weis, William I., Bachhawat, Priti, Kobilka, Tong Sun, Sexton, Patrick M., Kobilka, Brian K., Christopoulos, Arthur

“…Muscarinic M1–M5 acetylcholine receptors are G-protein-coupled receptors that regulate many vital functions of the central and peripheral nervous systems. In…”
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Aerosol and physical atmosphere model parameters are both important sources of uncertainty in aerosol ERF by Regayre, Leighton A, Johnson, Jill S, Yoshioka, Masaru, Pringle, Kirsty J, Sexton, David M. H, Booth, Ben B. B, Lee, Lindsay A, Bellouin, Nicolas, Carslaw, Kenneth S

“…Changes in aerosols cause a change in net top-of-the-atmosphere (ToA) short-wave and long-wave radiative fluxes; rapid adjustments in clouds, water vapour and…”
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The role of kinetic context in apparent biased agonism at GPCRs by Klein Herenbrink, Carmen, Sykes, David A., Donthamsetti, Prashant, Canals, Meritxell, Coudrat, Thomas, Shonberg, Jeremy, Scammells, Peter J., Capuano, Ben, Sexton, Patrick M., Charlton, Steven J., Javitch, Jonathan A., Christopoulos, Arthur, Lane, J. Robert

“…Biased agonism describes the ability of ligands to stabilize different conformations of a GPCR linked to distinct functional outcomes and offers the prospect…”
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Towards a structural understanding of allosteric drugs at the human calcium-sensing receptor by Leach, Katie, Gregory, Karen J, Kufareva, Irina, Khajehali, Elham, Cook, Anna E, Abagyan, Ruben, Conigrave, Arthur D, Sexton, Patrick M, Christopoulos, Arthur

“…Drugs that allosterically target the human calcium-sensing receptor （CaSR） have substantial therapeutic potential, but are currently limited. Given the absence…”
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Differential GLP-1R Binding and Activation by Peptide and Non-peptide Agonists by Zhang, Xin, Belousoff, Matthew J., Zhao, Peishen, Kooistra, Albert J., Truong, Tin T., Ang, Sheng Yu, Underwood, Christina Rye, Egebjerg, Thomas, Šenel, Petr, Stewart, Gregory D., Liang, Yi-Lynn, Glukhova, Alisa, Venugopal, Hari, Christopoulos, Arthur, Furness, Sebastian G.B., Miller, Laurence J., Reedtz-Runge, Steffen, Langmead, Christopher J., Gloriam, David E., Danev, Radostin, Sexton, Patrick M., Wootten, Denise

“…Peptide drugs targeting class B1 G-protein-coupled receptors (GPCRs) can treat multiple diseases; however, there remains substantial interest in the…”
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Allosteric GPCR modulators: taking advantage of permissive receptor pharmacology by Leach, Katie, Sexton, Patrick M, Christopoulos, Arthur

“…The past decade has witnessed a dramatic increase in the identification of allosteric modulators of G-protein-coupled receptor (GPCR) activity. Concomitantly,…”
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Allosteric modulation of G protein-coupled receptors by MAY, Lauren T, LEACH, Katie, SEXTON, Patrick M, CHRISTOPOULOS, Arthur

“…The past decade has witnessed a significant growth in the identification of allosteric modulators of G protein-coupled receptors (GPCRs), i.e., ligands that…”
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