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Key research papers

Walker, L.C., Berizzi, A.E., Chen, N.A., Rueda, P., Perreau, V.M., Huckstep, K., Srisontiyakul, J., Govitrapong, P., Xiaojian, J., Lindsley, C.W, Jones, C.K., Riddy, D. M., Christopoulos, A., Langmead C.J., and A.J. Lawrence  (2020) Acetylcholine muscarinic M4 receptors as a therapeutic target for alcohol use disorder: Converging evidence from humans and rodents. Biol. Psych. In Press.

Bradley, S.J., Molloy, C., Valuskova, P., Dwomoh, L., Scarpa, M., Rossi, M., Finlayson, L., Svensson, K.A., Chernet, E., Barth, V.N., Gherbi, K., Sykes, D.A., Wilson, C., Mistry, R., Sexton, P.M., Christopoulos, A., Mogg, A.J., Rosethorne, E.M., Sakata, S., Challiss, R.A.J., Broad L.M., and A.B. Tobin (2020) Chemogenetic and G protein-biased mice reveal importance of phosphorylation-dependent signalling in the design of next generation M1-muscarinic receptor ligands. Nature Chem. Biol. 16: 240-249.

DiCello, J.J., Carbone, S.E., Saito, A., Rajasekhar, P., Ceredig, R.A., Pham, V. Valant, C., Christopoulos, A., Veldhuis, N.A., Canals, M., Massotte, D., and D.P. Poole (2020) Mu and delta opioid receptors are coexpressed and functionally interact in the enteric nervous system of the mouse colon. Cell. Molec. Gastroenterol. Hepatol. 9: 465-483

Zhao, P., Liang, Y.L., Belousoff, M.J., Deganutti, G., Fletcher, M.M., Willard, F.S., Sloop, K.W., Inoue, A., Truong, T.T., Clydesdale, L., Furness, S.G.B., Christopoulos, A., Wang, M.W., Miller, L.J., Reynolds, C.A., Danev, R., Sexton, P.M., and D. Wootten (2020) Activation of GLP-1 receptor by a non-peptide agonist. Nature 577: 432-436.

Vuckovic Z., Gentry P.R., Berizzi A.E., Hirata K., Varghese S., Thompson G., van der Westhuizen E.T., Burger W.A.C., Rahmani R., Valant C., Langmead C.J., Lindsley C.W., Baell J.B., Tobin A.B., Sexton P.M., Christopoulos A., and D.M. Thal (2019) Crystal structure of the M5 muscarinic acetylcholine receptor. Proc Natl Acad Sci (USA) 116: 26001-26007.

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.*, and R.O. Dror (2019) Cryptic pocket formation underlies allosteric modulator selectivity at muscarinic GPCRs. Nature Comm 10: 3289. *Co-corresponding.

Jorg M., van der Westhuizen E.T., Khajehali E., Burger W.A.C., White J.M., Choy K.H.C., Tobin A.B., Sexton P.M., Valant C., Capuano B., Christopoulos A., and P.J. Scammells (2019) 6-Phenylpyrimidin-4-ones as Positive Allosteric Modulators at the M1 mAChR: The Determinants of Allosteric Activity. ACS Chem Neurosci 10: 1099-1114.

Draper-Joyce, C.J., Khosouei, M., Thal. D.M., Liang, Y.L., Nguyen, A.T.N., Furness, S.G.B., Venugopal, H., Baltos, J., Plitzko, J.P., Danev, R., Baumeisterm W., May, L.T., Wootten, D., Sexton, P.M., Glukhova, A. and A. Christopoulos (2018) Structure of the adenosine-bound human A1 receptor-Gi complex. Nature 558: 559-563.

Liang, Y.L., Khoshouei, M., Deganuti, G., Glukhova, A., Koole, C., Peat, T.S., Radjainia, M., Plitzko, J.M., Baumeister, W., Miller, L.M., Hay, D.L., Christopoulos, A., Reynolds, C.A., Wootten, D. and P M. Sexton (2018) Cryo-EM structure of the active, Gs-protein complexed, human CGRP receptor. Nature 561: 492-497.

Berizzi, A., Perry, C., Shackleford, D., Lindsley, C., Jones, C., Chen, N., Sexton, P.M., Christopoulos, A.*, Langmead, C.J. and A.J. Lawrence (2018) Muscarinic M5 receptors modulate ethanol seeking in rats. Neuropsychopharmacol., 43: 1510-1517. *Co-corresponding.

Korczynska, M., Clark, M.J., Valant, C.†, Moo, E.V., Abold, S., Weiss, D.R., Torosyan, H., Huang, W., Kruse, A.C., May, L.T., Baltos, J., Sexton, P.M., Kobilka, B.K., Christopoulos, A.*, Shoichet, B.K., and R.K. Sunahara (2018) Structure-based discovery of selective positive allosteric modulators of antagonists for the M2 muscarinic acetylcholine receptor. Proc. Nat. Acad. Sci. (USA) 115: E2419-E2428. †Co-first; *Co-corresponding.

Liang, Y.-L., Khosouei, M., Glukhova, A., Furness, S.G.B., Clydesdale, L., Koole, C., Troung, T.T., Thal, D.M., Lei, S., Radjainia, M., Danev, R., Baumeister, W., Wang, M.-W., Christopoulos, A., Sexton, P.M. and D. Wootten (2018) Phase-plate cryo-EM structure of a biased agonist-bound human GLP-1 receptor-Gs complex. Nature 555: 121-125.

Liang, Y.L., Khoshouei, M., Radjainia, M., Zhang, Y., Glukhova, A., Tarrasch, J., Thal, D.M., Furness, S.G.B., Christopoulos, G., Coudrat, T., Danev, R., Baumeister, W., Miller, LJ., Christopoulos, A., Kobilka, B.K., Wootten, D., Skiniotis, G. and P.M. Sexton (2017) Phase-plate cryo-EM structure of a class B GPCR-G protein complex. Nature 546: 118-123.

Glukhova, A., Thal, D.T., Nguyen, A.T.N., Vecchio, E.A., Jörg, M., Scammells, P.J., May, L.T., Sexton, P.M. and A. Christopoulos (2017) Structure of the adenosine A1 receptor reveals the basis for subtype selectivity. Cell 168: 867-877.

Bradley, S.J., Bourgognon, J.-M.,Sanger, H.E., Verity, N.,Mogg, A., White, D.J., Butcher, A.J., Moreno,J.A.,Molloy,C.,Macedo-Hatch, T., Edwards, J.E., Wess, J., Pawlak, R., Read, D.J., Sexton, P.M., Broad, L.M., Steinert, J.R., Mallucci, G.R., Christopoulos, A., Felder, C.C. and A.B. Tobin (2017) M1-muscarinic allosteric modulators slow prion neurodegeneration and restore memory loss. J. Clin. Invest. 127: 487-499.

Qin, R.C.X., May, L.T., Li, R., Cao, N., Rosli, S., Deo, M., Alexander, A.E., Horlock, D., Bourke, J.E., Yang, Y.H., Stewart, A.G., Kaye, D.M., Du, X.-J., Sexton, P.M., Christopoulos, A., Gao X.-M. and R. H. Ritchie (2017) Small-molecule biased formyl peptide receptor agonist Compound-17b protects against myocardial ischemia-reperfusion injury in mice. Nature Comm. 8: 14232.

Furness, S.G.B., Liang, Y.-L., Nowell, C.J., Halls, M.L., Wookey, P.J., Dal Maso, E., Inoue, A., Christopoulos, A., Wootten, D. and P.M. Sexton (2016) Ligand-dependent modulation of G protein conformation alters drug efficacy. Cell. 167: 739-749.

Miao, Y., Goldfeld, D., Moo, E.V., Sexton, P.M., Christopoulos, A., McCammon, A.J. and C. Valant (2016) Accelerated structure-based design of chemically diverse allosteric modulators of a muscarinic G protein-coupled receptor. Proc. Nat. Acad. Sci. (USA). 113: E5675-E5684.

Wootten, D., Reynolds, C.A., Smith, K.J., Mobarec, J.C., Koole, C., Savage, E., Pabreja, K., Simms, J., Sridhar, R., Furness, S.G.B., Liu, M., Thompson, P.E., Miller, L.J., Christopoulos, A. and P.M. Sexton (2016) The GLP-1 receptor extracellular surface is a molecular trigger for biased agonism. Cell. 165: 1632-1643.

Leach, K., Gregory, K.J., Kufareva, I., Khajehali, E., Cook, A.E., Abagyan, R., Conigrave, A.D., Sexton P.M. and A. Christopoulos (2016) Towards a structural understanding of allosteric drugs at the human calcium sensing receptor Cell Res. 26: 574-592.

Klein Herenbrink, C., Sykes, D.A., Donthamsetti, P., Canals, M., Coudrat, T., Shonberg, J., Scammells, P.J., Capuano, B., Sexton, P.M., Charlton, S.J., Javitch, J.A., Christopoulos, A.* and J.R. Lane (2016) The role of kinetic context in apparent biased agonism at GPCRs.  Nature Comm. 7: 10842 *Co-corresponding.

Thal, D.M., Sun, B., Feng, D., Nawaratne, V., Leach, K., Felder, C.C., Bures, M.G., Evans, D.A., Weis, W.I., Bachhawat, P., Kobilka, T.S., Sexton, P.M., Kobilka, B.M. and A. Christopoulos (2015) Crystal structures of the M1 and M4 muscarinic acetylcholine receptors and insights into their allosteric modulation. Nature. 531: 335–340.

Lane, J.R., Donthamsetti, P., Shonberg, J., Draper-Joyce, C.J., Dentry, S., Michino, M., Shi, L., López, L., Scammells, P.J., Capuano, B., Sexton, P.M., Javitch, J.A. and A. Christopoulos (2014) A new mechanism of allostery in a G protein-coupled receptor dimer. Nature Chem. Biol. 10: 745-752.

Valant, C., May, L.T., Aurelio, L., Chuo, C.H., White, P.J., Baltos, J., Sexton, P.M., Scammells, P.J. and A. Christopoulos (2014) Separation of on-target efficacy from adverse effects through rational design of a bitopic adenosine receptor agonist. Proc. Nat. Acad. Sci. (USA)111: 4614-4619.

Dror, R.O., Green, H.F., Valant, C.†, Borhani, D.W., Valcourt, J.R., Pan, A.C., Arlow, D.H., Canals, M., Lane, J.R., Rahmani, R., Baell, J.B., Sexton, P.M., Christopoulos, A*. and D.E. Shaw (2013) Structural basis for modulation of a G-protein-coupled receptor by allosteric drugs. Nature. 503: 295-299.†Co-first; *Co-corresponding.

Kruse, A.C., Ring, A.M., Manglik, A., Hu, J., Hu, K., Eitel, K., Hübner, H., Pardon, E., Valant, C., Sexton, P.M., Christopoulos, A., Felder, C.C., Gmeiner, P., Steyert, J., Weiss, W.I., Garcia, K.C., Wess, J. and B.K. Kobilka (2013) Activation and allosteric modulation of a muscarinic acetylcholine receptor. Nature. 504: 101-106.

Mistry, S., Valant, C., Sexton, P., Capuano, B., Christopoulos, A.* and P.J. Scammells (2013) Synthesis and pharmacological profiling of analogues of BQCA as allosteric modulators of the M1 muscarinic receptor. J. Med. Chem. 56: 5151-5172. *Co-corresponding.

Leach, K., Wen, A., Cook, A.E., Sexton, P.M., Conigrave, A.D, and A. Christopoulos (2013) Impact of clinically relevant mutations on the pharmacoregulation and signaling bias of the calcium sensing receptor by positive and negative allosteric modulators. Endocrinology154: 1105-1116.

Gregory, K.J., Sexton, P.M., Tobin, A.B. and A. Christopoulos (2012) Stimulus bias provides evidence for conformational constraints in the structure of a G protein-coupled receptor. J. Biol. Chem. 287: 37066-37077.

Kenakin, T., Watson, C., Muniz-Medina, V. and A. Christopoulos (with Appendix by S. Watson) (2012) A simple method to quantify functional selectivity and agonist bias. ACS Chem. Neurosci. 3: 193-203.

Wootten D., Savage E.E., Valant C., May L.T., Sloop K.W., Ficorilli J., Showalter A.D., Willard F.S., Christopoulos A. and P.M. Sexton. Allosteric modulation of endogenous metabolites as an avenue for drug discovery.Mol Pharmacol., 2012, 82(2):281-90.

Valant, C., Felder, C.C., Sexton, P.M. and A. Christopoulos (2012) Probe-dependence in the allosteric modulation of a G protein-coupled receptor:  Implications for detection and validation of allosteric ligand effects.  Mol. Pharmacol. 81: 41-52.

Canals, M., Lane, J.R., Wen, A., Scammells, P.J., Sexton, P.M. and A. Christopoulos (2012) A Monod-Wyman-Changeux mechanism can explain G protein-coupled receptor (GPCR) allosteric modulation. J. Biol. Chem. 287: 650-659.

Valant, C., Gregory, K.J., Hall, N.E., Scammells, P.J., Lew, M.J., Sexton, P.M. and A. Christopoulos (2008) A novel mechanism of G protein-coupled receptor functional selectivity: muscarinic partial agonist McN-A-343 as a bitopic orthosteric/allosteric ligand, J. Biol. Chem, 283: 29312-29321.


Wootten, D., Christopoulos, A., Solano, M.M., Babu, M.M., and P.M. Sexton (2018) Mechanisms of signalling and bias in G-protein coupled receptors. Nature Rev. Mol. Cell Biol. 19: 638-653.

Thal, D.M., Glukhova, A., Sexton P.M. and A. Christopoulos (2018) Structural insights into G-protein-coupled receptor allostery. Nature 559: 45-53.

Thal D.M., Vuckovic Z., Draper-Joyce C.J., Liang Y.L., Glukhova A., Christopoulos A., Sexton P.M. (2018) Recent advances in the determination of G protein-coupled receptor structures. Curr Opin Struct Biol 51: 28-34

Lane, J.R., May, L.T., Parton, R.G., Sexton, P.M and A. Christopoulos (2017) A kinetic view of GPCR allostery and biased agonism. Nature Chem. Biol. 13: 929-937.

Wootten, D., Miller, L.J., Koole, C, Christopoulos, A. and P.M. Sexton (2017) Allostery and biased agonism at class B G protein-coupled receptors. Chem. Rev. 117: 111-138.

Changeux, J.P. and A. Christopoulos (2016) Allosteric modulation as a unifying mechanism for receptor function and regulation. Cell. 166: 1084-1102.

van der Westhuizen E.T., Valant C., Sexton P.M. and A. Christopoulos. Endogenous allosteric modulators of G protein-coupled receptors. J. Pharm. Exp. Ther. 2015, 353: 246–260.

Gentry, P.R., Sexton, P.M. and A. Christopoulos (2015) Novel allosteric modulators of G protein-coupled receptors. J. Biol. Chem. 290: 19478-19488.

Christopoulos, A. (2014) Advances in GPCR allostery: From function to structure.  Mol. Pharmacol. 86: 463-478.

Christopoulos, A., Changeux, J.P., Catterall, W.A., Fabbro, D., Burris, T.P., Cidlowski, J.A., Olsen, R.W., Peters, J.A., Neubig, R.R., Pin, J.P., Sexton, P.M., Kenakin, T.P., Ehlert, F.J., Spedding M. and C.J. Langmead (2014) International Union of Basic and Clinical Pharmacology. XC. Multi-site Pharmacology: Recommendations for the nomenclature of receptor allosterism and allosteric ligands. Pharmacol. Rev. 66: 918-947.

Kruse, A.C., Kobilka, B.K., Gautam,D.,Sexton, P.M., Christopoulos, A. and J., Wess (2014) Insights into muscarinic acetylcholine receptor biology, pharmacology, and structure. Nature Rev. Drug Discovery, 13: 549-560.

Kenakin, T. and A. Christopoulos (2013) Signaling bias in new drug discovery: Detection, quantification and therapeutic impact. Nature Rev. Drug Discovery 12: 205–216.

Valant, C., Lane, J.R., Sexton, P.M. and A. Christopoulos (2012) The best of both worlds? Bitopic orthosteric/allosteric ligands of G protein-coupled receptors. Ann. Rev. Pharmacol. Toxicol., 52: 153-178.

Wootten, D., Christopoulos, A. and P.M. Sexton (2013) Emerging paradigms in GPCR allostery: Implications for drug discovery. Nature Rev. Drug Discovery 12: 630-644.

Keov, P., Sexton, P.M. and A. Christopoulos (2011) Allosteric modulation of G protein-coupled receptors: A pharmacological perspective. Neuropharmacol. 60: 24-35.

Kenakin, T. and A. Christopoulos (2011) Analytical pharmacology: The impact of numbers on pharmacology. Trends Pharmacol. Sci. 32: 189-196.

Conn, P.J., Christopoulos, A. and C.W. Lindsley (2009) Allosteric modulators of GPCRs: A novel approach for the treatment of CNS disorders. Nature Rev. Drug Discovery 8: 41-54.

Leach, K., Sexton, P.M. and A. Christopoulos (2007) Allosteric modulators of GPCRs: Taking advantage of permissive receptor pharmacology. Trends Pharmacol. Sci. 28: 382-389.

May, L.T., Leach, K., Sexton, P.M. and A. Christopoulos (2007) Allosteric modulation of G protein-coupled receptors, Ann. Rev. Pharmacol. Toxicol., 47: 1-51.

Christopoulos, A. and T. Kenakin (2002) G protein-coupled receptor allosterism and complexing, Pharmacol. Rev. 54: 323-374.

Christopoulos, A. (2002) Allosteric binding sites on cell-surface receptors: Novel targets for drug discovery. Nature Rev. Drug Discovery 1: 198-210.