1986 …2023
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Research Output 1986 2019

2019

6-Phenylpyrimidin-4-ones as Positive Allosteric Modulators at the M1 mAChR: The Determinants of Allosteric Activity

Jorg, M. T., van der Westhuizen, E. T., Khajehali, E., Burger, W. A. C., White, J., Choy, K. H. C., Tobin, A. B., Sexton, P. M., Valant, C., Capuano, B., Christopoulos, A. & Scammells, P. J., 20 Mar 2019, In : ACS Chemical Neuroscience. 10, 3, p. 1099-1114 16 p.

Research output: Contribution to journalArticleResearchpeer-review

Cryptic pocket formation underlies allosteric modulator selectivity at muscarinic GPCRs

Hollingsworth, S. A., Kelly, B., Valant, C., Michaelis, J. A., Mastromihalis, O., Thompson, G., Venkatakrishnan, A. J., Hertig, S., Scammells, P. J., Sexton, P. M., Felder, C. C., Christopoulos, A. & Dror, R. O., 1 Dec 2019, In : Nature Communications. 10, 1, p. 1-9 9 p., 3289.

Research output: Contribution to journalArticleResearchpeer-review

Open Access
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Deconvoluting the Molecular Control of Binding and Signaling at the Amylin 3 Receptor: RAMP3 Alters Signal Propagation through Extracellular Loops of the Calcitonin Receptor

Pham, V., Zhu, Y., Dal Maso, E., Reynolds, C. A., Deganutti, G., Atanasio, S., Hick, C. A., Yang, D., Christopoulos, A., Hay, D. L., Furness, S. G. B., Wang, M-W., Wootten, D. & Sexton, P. M., 18 Mar 2019, In : ACS Pharmacology and Translational Sciences. 2, 3, p. 183-197 15 p.

Research output: Contribution to journalArticleResearchpeer-review

4 Citations (Scopus)

Drug-receptor kinetics and sigma-1 receptor affinity differentiate clinically evaluated histamine H3 receptor antagonists

Riddy, D. M., Cook, A. E., Shackleford, D. M., Pierce, T. L., Mocaer, E., Mannoury la Cour, C., Sors, A., Charman, W. N., Summers, R. J., Sexton, P. M., Christopoulos, A. & Langmead, C. J., 1 Jan 2019, In : Neuropharmacology. 144, p. 244-255 12 p.

Research output: Contribution to journalArticleResearchpeer-review

Open Access
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1 Citation (Scopus)

Expression and activity of the calcitonin receptor family in a sample of primary human high-grade gliomas

Ostrovskaya, A., Hick, C., Hutchinson, D. S., Stringer, B. W., Wookey, P. J., Wootten, D., Sexton, P. M. & Furness, S. G. B., 18 Feb 2019, In : BMC Cancer. 19, 1, 12 p., 157.

Research output: Contribution to journalArticleResearchpeer-review

Open Access
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Light-activated chimeric GPCRs: limitations and opportunities

Tichy, A-M., Gerrard, E. J., Sexton, P. M. & Janovjak, H., 1 Aug 2019, In : Current Opinion in Structural Biology. 57, p. 196-203 8 p.

Research output: Contribution to journalReview ArticleResearchpeer-review

Molecular Basis of Action of a Small-Molecule Positive Allosteric Modulator Agonist at the Type 1 Cholecystokinin Holoreceptor

Desai, A. J., Mechin, I., Nagarajan, K., Valant, C., Wootten, D., Lam, P. C. H., Orry, A., Abagyan, R., Nair, A., Sexton, P. M., Christopoulos, A. & Miller, L. J., 1 Mar 2019, In : Molecular Pharmacology. 95, 3, p. 245-259 15 p.

Research output: Contribution to journalArticleResearchpeer-review

O-GlcNAc Engineering of GPCR Peptide-Agonists Improves Their Stability and in Vivo Activity

Levine, P. M., Balana, A. T., Sturchler, E., Koole, C., Noda, H., Zarzycka, B., Daley, E. J., Truong, T., Katritch, V., Gardella, T. J., Wootten, D., Sexton, P. M., McDonald, P. & Pratt, M. R., 11 Sep 2019, In : Journal of the American Chemical Society. 141, 36, p. 14210-14219 10 p.

Research output: Contribution to journalArticleResearchpeer-review

The Molecular Control of Calcitonin Receptor Signaling

dal Maso, E., Glukhova, A., Zhu, Y., Garcia-Nafria, J., Tate, C. G., Atanasio, S., Reynolds, C. A., Ramirez-Aportela, E., Carazo, J-M., Hick, C. A., Furness, S. G. B., Hay, D. L., Liang, Y-L., Miller, L. J., Christopoulos, A., Wang, M-W., Wootten, D. & Sexton, P. M., 11 Jan 2019, In : ACS Pharmacology and Translational Sciences. 2, 1, p. 31-51 21 p.

Research output: Contribution to journalArticleResearchpeer-review

Use of Backbone Modification to Enlarge the Spatiotemporal Diversity of Parathyroid Hormone Receptor-1 Signaling via Biased Agonism

Liu, S., Jean-Alphonse, F. G., White, A. D., Wootten, D., Sexton, P. M., Gardella, T. J., Vilardaga, J. P. & Gellman, S. H., 18 Sep 2019, In : Journal of the American Chemical Society. 141, 37, p. 14486-14490 5 p.

Research output: Contribution to journalArticleResearchpeer-review

4 Citations (Scopus)

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

Bradley, S. J., Molloy, C., Bundgaard, C., Mogg, A. J., Thompson, K. J., Dwomoh, L., Sanger, H. E., Crabtree, M. D., Brooke, S. M., Sexton, P. M., Felder, C. C., Christopoulos, A., Broad, L. M., Tobin, A. B. & Langmead, C. J., 1 Jun 2018, In : Molecular Pharmacology. 93, 6, p. 645-656 12 p.

Research output: Contribution to journalArticleResearchpeer-review

Open Access
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2 Citations (Scopus)

Characterization of signalling and regulation of common calcitonin receptor splice variants and polymorphisms

Dal Maso, E., Just, R., Hick, C., Christopoulos, A., Sexton, P. M., Wootten, D. & Furness, S. G. B., 1 Feb 2018, In : Biochemical Pharmacology. 148, p. 111-129 19 p.

Research output: Contribution to journalArticleResearchpeer-review

25 Citations (Scopus)

Cryo-EM structure of the active, Gs-protein complexed, human CGRP receptor

Liang, Y-L., Khoshouei, M., Deganutti, G., Glukhova, A., Koole, C., Peat, T. S., Radjainia, M., Plitzko, J. M., Baumeister, W., Miller, L. J., Hay, D. L., Christopoulos, A., Reynolds, C. A., Wootten, D. & Sexton, P. M., 27 Sep 2018, In : Nature. 561, 7724, p. 492-497 6 p.

Research output: Contribution to journalArticleResearchpeer-review

3 Citations (Scopus)
2 Citations (Scopus)

Discovery and Optimization of Potent and CNS Penetrant M5-Preferring Positive Allosteric Modulators Derived from a Novel, Chiral N-(Indanyl)piperidine Amide Scaffold

Bender, A. M., Cho, H. P., Nance, K. D., Lingenfelter, K. S., Luscombe, V. B., Gentry, P. R., Voigtritter, K., Berizzi, A. E., Sexton, P. M., Langmead, C. J., Christopoulos, A., Locuson, C. W., Bridges, T. M., Chang, S., O'Neill, J. C., Zhan, X., Niswender, C. M., Jones, C. K., Conn, P. J. & Lindsley, C. W., 18 Jul 2018, In : ACS Chemical Neuroscience. 9, 7, p. 1572-1581 10 p.

Research output: Contribution to journalArticleResearchpeer-review

3 Citations (Scopus)

Divergent effects of strontium and calcium-sensing receptor positive allosteric modulators (calcimimetics) on human osteoclast activity

Diepenhorst, N. A., Leach, K., Keller, A. N., Rueda, P., Cook, A. E., Pierce, T. L., Nowell, C., Pastoureau, P., Sabatini, M., Summers, R. J., Charman, W. N., Sexton, P. M., Christopoulos, A. & Langmead, C. J., 1 Nov 2018, In : British Journal of Pharmacology. 175, 21, p. 4095-4108 14 p.

Research output: Contribution to journalArticleResearchpeer-review

7 Citations (Scopus)

Extracellular loops 2 and 3 of the calcitonin receptor selectively modify agonist binding and efficacy

Dal Maso, E., Zhu, Y., Pham, V., Reynolds, C. A., Deganutti, G., Hick, C. A., Yang, D., Christopoulos, A., Hay, D. L., Wang, M. W., Sexton, P. M., Furness, S. G. B. & Wootten, D., 1 Apr 2018, In : Biochemical Pharmacology. 150, p. 214-244 31 p.

Research output: Contribution to journalArticleResearchpeer-review

Open Access
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5 Citations (Scopus)

Glucagon-like peptide-1 receptor internalisation controls spatiotemporal signalling mediated by biased agonists

Fletcher, M. M., Halls, M. L., Zhao, P., Clydesdale, L., Christopoulos, A., Sexton, P. M. & Wootten, D., 1 Oct 2018, In : Biochemical Pharmacology. 156, p. 406-419 14 p.

Research output: Contribution to journalArticleResearchpeer-review

15 Citations (Scopus)

G protein–coupled receptors targeting insulin resistance, obesity, and type 2 diabetes mellitus

Riddy, D. M., Delerive, P., Summers, R. J., Sexton, P. & Langmead, C. J., 1 Jan 2018, In : Pharmacological Reviews. 70, 1, p. 39-67 29 p.

Research output: Contribution to journalReview ArticleResearchpeer-review

40 Citations (Scopus)

Mechanisms of signalling and biased agonism in G protein-coupled receptors

Wootten, D. L., Christopoulos, A., Marti-Solano, M., Babu, M. M. & Sexton, P. M., Oct 2018, In : Nature Reviews Molecular Cell Biology. 19, 10, p. 638-653 16 p.

Research output: Contribution to journalReview ArticleResearchpeer-review

Open Access
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9 Citations (Scopus)

Muscarinic M5 receptors modulate ethanol seeking in rats

Berizzi, A. E., Perry, C. J., Shackleford, D. M., Lindsley, C. W., Jones, C. K., Chen, N. A., Sexton, P. M., Christopoulos, A., Langmead, C. J. & Lawrence, A. J., 1 Jun 2018, In : Neuropsychopharmacology. 43, 7, p. 1510-1517 8 p.

Research output: Contribution to journalArticleResearchpeer-review

Open Access
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71 Citations (Scopus)

Phase-plate cryo-EM structure of a biased agonistbound human GLP-1 receptor-Gs complex

Liang, Y. L., Khoshouei, M., Glukhova, A., Furness, S. G. B., Zhao, P., Clydesdale, L., Koole, C., Truong, T. T., Thal, D. M., Lei, S., Radjainia, M., Danev, R., Baumeister, W., Wang, M. W., Miller, L. J., Christopoulos, A., Sexton, P. M. & Wootten, D., 1 Mar 2018, In : Nature. 555, 7694, p. 121-125 5 p.

Research output: Contribution to journalArticleResearchpeer-review

Open Access
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2 Citations (Scopus)

Probing the binding site of novel selective positive allosteric modulators at the M1 muscarinic acetylcholine receptor

Khajehali, E., Valant, C., Jörg, M., Tobin, A. B., Conn, P. J., Lindsley, C. W., Sexton, P. M., Scammells, P. J. & Christopoulos, A., 1 Aug 2018, In : Biochemical Pharmacology. 154, p. 243-254 12 p.

Research output: Contribution to journalArticleResearchpeer-review

Open Access
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13 Citations (Scopus)

Rules of Engagement: GPCRs and G Proteins

Glukhova, A., Draper-Joyce, C. J., Sunahara, R. K., Christopoulos, A., Wootten, D. L. & Sexton, P. M., 7 Sep 2018, In : ACS Pharmacology and Translational Sciences. 1, 2, p. 73-83 11 p.

Research output: Contribution to journalReview ArticleResearchpeer-review

48 Citations (Scopus)

Structural insights into G-protein-coupled receptor allostery

Thal, D. M., Glukhova, A., Sexton, P. M. & Christopoulos, A., 5 Jul 2018, In : Nature. 559, 7712, p. 45-53 9 p.

Research output: Contribution to journalReview ArticleResearchpeer-review

2 Citations (Scopus)

Structure-Activity Relationships of Pan-Gαq/11 Coupled Muscarinic Acetylcholine Receptor Positive Allosteric Modulators

Berizzi, A. E., Bender, A. M., Lindsley, C. W., Conn, P. J., Sexton, P. M., Langmead, C. J. & Christopoulos, A., 18 Jul 2018, In : ACS Chemical Neuroscience. 9, 7, p. 1818-1828 11 p.

Research output: Contribution to journalArticleResearchpeer-review

13 Citations (Scopus)

Structure-based discovery of selective positive allosteric modulators of antagonists for the M2 muscarinic acetylcholine receptor

Korczynska, M., Clark, M. J., Valant, C., Xu, J., Moo, E. V., Albold, S., Weiss, D. R., Torosyan, H., Huang, W., Kruse, A. C., Lyda, B. R., May, L. T., Baltos, J. A., Sexton, P. M., Kobilka, B. K., Christopoulos, A., Shoichet, B. K. & Sunahara, R. K., 6 Mar 2018, In : Proceedings of the National Academy of Sciences. 115, 10, p. E2419-E2428 10 p.

Research output: Contribution to journalArticleResearchpeer-review

Open Access
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60 Citations (Scopus)

Structure of the adenosine-bound human adenosine A1 receptor-Gi complex

Draper-Joyce, C. J., Khoshouei, M., Thal, D. M., Liang, Y. L., Nguyen, A. T. N., Furness, S. G. B., Venugopal, H., Baltos, J. A., Plitzko, J. M., Danev, R., Baumeister, W., May, L. T., Wootten, D., Sexton, P. M., Glukhova, A. & Christopoulos, A., 20 Jun 2018, In : Nature. 558, 7711, p. 559-565 7 p.

Research output: Contribution to journalArticleResearchpeer-review

6 Citations (Scopus)

To Bind or Not to Bind: Unravelling GPCR Polypharmacology

Sexton, P. M. & Christopoulos, A., 8 Feb 2018, In : Cell. 172, 4, p. 636-638 3 p.

Research output: Contribution to journalShort SurveyOtherpeer-review

Open Access
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5 Citations (Scopus)

Toward an understanding of the structural basis of allostery in muscarinic acetylcholine receptors

Burger, W. A. C., Sexton, P. M., Christopoulos, A. & Thal, D. M., 1 Oct 2018, In : Journal of General Physiology. 150, 10, p. 1360-1372 13 p.

Research output: Contribution to journalArticleResearchpeer-review

3 Citations (Scopus)

Two distinct domains of the glucagon-like peptide-1 receptor control peptide-mediated biased agonism

Lei, S., Clydesdale, L., Dai, A., Cai, X., Yang, F., Yang, D., Liang, Y-L., Koole, C., Zhao, P., Coudrat, T., Christopoulos, A., Wang, M-W., Wootten, D. & Sexton, P. M., 1 Jan 2018, In : Journal of Biological Chemistry. 293, 24, p. 9370-9387 18 p.

Research output: Contribution to journalArticleResearchpeer-review

4 Citations (Scopus)

Vascular and molecular pharmacology of the metabolically stable CGRP analogue, SAX

Sheykhzade, M., Abdolalizadeh, B., Koole, C., Pickering, D. S., Dreisig, K., Johansson, S. E., Abboud, B. K., Dreier, R., Berg, J. O., Jeppesen, J. L., Sexton, P. M., Edvinsson, L., Wootten, D. & Sams, A., 15 Jun 2018, In : European Journal of Pharmacology. 829, p. 85-92 8 p.

Research output: Contribution to journalArticleResearchpeer-review

2017
42 Citations (Scopus)

A kinetic view of GPCR allostery and biased agonism

Lane, J. R., May, L. T., Parton, R. G., Sexton, P. M. & Christopoulos, A., 18 Aug 2017, In : Nature Chemical Biology. 13, 9, p. 929-937 9 p.

Research output: Contribution to journalReview ArticleResearchpeer-review

Open Access
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33 Citations (Scopus)

Allostery and Biased Agonism at Class B G Protein-Coupled Receptors

Wootten, D., Miller, L. J., Koole, C., Christopoulos, A. & Sexton, P. M., 11 Jan 2017, In : Chemical Reviews. 117, 1, p. 111-138 28 p.

Research output: Contribution to journalReview ArticleResearchpeer-review

13 Citations (Scopus)

Characterization of signal bias at the GLP-1 receptor induced by backbone modification of GLP-1

Hager, M. V., Clydesdale, L., Gellman, S. H., Sexton, P. M. & Wootten, D., 15 Jul 2017, In : Biochemical Pharmacology. 136, p. 99-108 10 p.

Research output: Contribution to journalArticleResearchpeer-review

1 Citation (Scopus)

Coding GPCR-G protein specificity

Furness, S. G. B. & Sexton, P. M., 1 Oct 2017, In : Cell Research. 27, 10, p. 1193-1194 2 p.

Research output: Contribution to journalShort SurveyResearchpeer-review

Open Access
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3 Citations (Scopus)

Co-expressed class B G protein-coupled secretin and GLP-1 receptors self- and cross-associate: impact on pancreatic islets

Harikumar, K. G., Lau, S., Sexton, P. M., Wootten, D. & Miller, L. J., 1 Jun 2017, In : Endocrinology. 158, 6, p. 1685-1700 16 p.

Research output: Contribution to journalArticleResearchpeer-review

20 Citations (Scopus)

Genetically encoded photocross-linkers determine the biological binding site of exendin-4 peptide in the N-terminal domain of the intact human glucagon-like peptide-1 receptor (GLP-1R)

Koole, C., Reynolds, C. A., Mobarec, J. C., Hick, C., Sexton, P. M. & Sakmar, T. P., 28 Apr 2017, In : Journal of Biological Chemistry. 292, 17, p. 7131-7144 14 p.

Research output: Contribution to journalArticleResearchpeer-review

Open Access
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2 Citations (Scopus)

High throughput, quantitative analysis of human osteoclast differentiation and activity

Diepenhorst, N., Nowell, C., Rueda, P., Henriksen, K., Pierce, T., Cook, A., Pastoureau, P., Sabatini, M., Charman, W., Christopoulos, A., Summers, R., Sexton, P. & Langmead, C., 15 Feb 2017, In : Analytical Biochemistry. 519, p. 51-56 6 p.

Research output: Contribution to journalArticleResearchpeer-review

3 Citations (Scopus)

Improving virtual screening of G protein-coupled receptors via ligand-directed modeling

Coudrat, T., Simms, J., Christopoulos, A., Wootten, D. & Sexton, P. M., 1 Nov 2017, In : PLoS Computational Biology. 13, 11, 40 p., e1005819.

Research output: Contribution to journalArticleResearchpeer-review

Open Access
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10 Citations (Scopus)

Isoform-specific biased agonism of histamine H3 receptor agonists

Riddy, D. M., Cook, A. E., Diepenhorst, N. A., Bosnyak, S., Brady, R., La Cour, C. M., Mocaer, E., Summers, R. J., Charman, W. N., Sexton, P. M., Christopoulos, A. & Langmead, C. J., 1 Feb 2017, In : Molecular Pharmacology. 91, 2, p. 87-99 13 p.

Research output: Contribution to journalArticleResearchpeer-review

20 Citations (Scopus)

M1 muscarinic allosteric modulators slow prion neurodegeneration and restore memory loss

Bradley, S. J., Bourgognon, J. M., Sanger, H. E., Verity, N., Mogg, A. J., White, D. J., Butcher, A. J., Moreno, J. A., Molloy, C., Macedo-Hatch, T., Edwards, J. M., Wess, J., Pawlak, R., Read, D. J., Sexton, P. M., Broad, L. M., Steinert, J. R., Mallucci, G. R., Christopoulos, A., Felder, C. C. & 1 others, Tobin, A. B., 1 Feb 2017, In : Journal of Clinical Investigation. 127, 2, p. 487-499 13 p.

Research output: Contribution to journalArticleResearchpeer-review

Open Access
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170 Citations (Scopus)

Phase-plate cryo-EM structure of a class B GPCR-G-protein complex

Liang, Y-L., Khoshouei, M., Radjainia, M., Zhang, Y., Glukhova, A., Tarrasch, J., Thal, D., Furness, S. G. B., Christopoulos, G., Coudrat, T., Danev, R., Baumeister, W., Miller, L. J., Christopoulos, A., Kobilka, B., Wootten, D., Skiniotis, G. & Sexton, P., 1 Jun 2017, In : Nature. 546, 7656, p. 118-123 6 p.

Research output: Contribution to journalArticleResearchpeer-review