Professor Arthur Christopoulos - Researcher Profile

Arthur Christopoulos

Address

Faculty of Pharmacy and Pharmaceutical Sciences
381 Royal Parade, Parkville

Biography

Position

Professor of Pharmacology
Faculty of Pharmacy and Pharmaceutical Sciences

NHMRC Principal Research Fellow

Theme Leader - Drug Discovery Biology
Monash Institute of Pharmaceutical Sciences

An end to andlsquo;blunt hammer' medicines

Professor Arthur Christopoulos is working to end the reign of "blunt hammer" medicines. By targeting previously unappreciated drug recognition sites in the body, Arthur and his colleagues are developing medicines potent enough to offer better treatment of schizophrenia and diabetes, and selective enough to eliminate side-effects.

Key to the research at the Monash Drug Discovery Biology Laboratory is understanding the potential of 'allosteric' sites on G protein-coupled receptors (GPCRs), the largest drug target family in the human genome.

These GPCR allosteric sites have largely been ignored in traditional drug discovery approaches, but offer tremendous opportunity for researchers who can understand and exploit them.

"Nearly all drugs do one of two things - they either block something or they mimic something," Arthur says.

"But what they block and mimic are the body's own chemicals, which interact with highly conserved regions on the GPCRs. What we have found is that GPCRs have other, more variable, sites where the body's chemicals don't act, and we can make synthetic chemicals that target those other sites.

"In terms of the old 'lock and the key' view of how drugs work, we have basically found alternative, more flexible, locks," Arthur says.

Increasing drug selectivity is vital to eliminating medication side-effects.

Drugs that block or mimic the body's chemicals will act wherever those chemicals are found. So, if a drug is designed to target the body's chemical site in a brain protein, it may also act in the same region of the same protein in the heart. These are the "blunt hammers" Arthur is trying to eradicate.

In addition to reducing side-effects, targeting allosteric sites offers better ways of treating cognitive deficits in schizophrenia.

"One of the biggest problems with treating schizophrenia is that the anti-psychotic drugs on the market will treat the psychotic symptoms very well, but what they don't treat well are the so-called negative symptoms, such as withdrawal or apathy, or the cognitive memory effects" Arthur says.

"It's an unmet medical need we are trying to fill. And we have found allosteric sites that are very selective to a family of proteins in the brain that have positive cognitive effects."

Arthur's work could also have positive consequences for adult-onset diabetes sufferers, potentially eliminating the need for regular injections.

Allosteric small-molecule compounds offer the potential for orally available tablets to reach the key diabetes drug targets currently only accessible with larger (injectible) peptides.

It is potential break-throughs like this that led Arthur into pharmacology research.

"I originally trained as a pharmacist, and I was working in a pharmacy while completing my PhD," he says.

"I saw at the front end what medications were available and, for many diseases, they're just not good enough. We are giving blunt hammers to the elderly who are particularly sensitive to the side effects of these medications, and our population is ageing, getting obese and more diabetic as well, so any way we can fine tune medications will be great for society.

"Now is the time for Monash to say we can contribute here, we can really turn our discoveries into something."

Related Links:

Keywords

Analytical Pharmacology; Allosteric Modulation; Receptor Theory, Commentary: Drug Discovery; Pharmaceutical Research; Drug Side-Effects; Psychiatric Drugs, Supervision: Molecular Pharmacology; Drug Discovery; Receptors and Signal Transduction

Qualifications

Unknown
Institution: Victorian College of Pharmacy
Year awarded: 1999

Publications

Book Chapters

Tschammer, N., Christopoulos, A., Kenakin, T.P., 2015, Allosteric modulation of chemokine receptors, in Chemokines: Chemokines and Their Receptors in Drug Discovery, eds Nuska Tschammer, Springer, Cham Switzerland, pp. 87-117.

Wootten, D.L., Tilakaratne, N., Christopoulos, A., Sexton, P., 2013, CGRP/adrenomedullin, in Handbook of Biologically Active Peptides, eds Abba J Kastin, Elsevier, San Diego CA USA, pp. 744-751.

Sexton, P.M., Poyner, D.R., Simms, J., Christopoulos, A., Hay, D.L., 2012, RAMPs as drug targets, in RAMPs, eds W.S. Spielman, & N. Parameswaran, Springer, USA, pp. 61-74.

Leach, K., Simms, J., Sexton, P.M., Christopoulos, A., 2012, Structure-function studies of muscarinic acetylcholine receptors, in Muscarinic Receptors - Handbook of Experimental Pharmacology 208, eds A D Fryer, A Christopoulos and N M Nathanson, Springer, USA, pp. 29-48.

Wootten, D., Simms, J.W., Hay, D.L., Christopoulos, A., Sexton, P., 2010, Receptor activity modifying proteins and their potential as drug targets, in Progress in Molecular Biology and Translational Science, eds C A Lunn, Academic Press, UK, pp. 53-79.

Simms, J.W., Hall, N.E., Lam, P.H., Christopoulos, A., Abagyan, R., Sexton, P., 2009, Homology Modeling of GPCRs, in Methods in Molecular Biology - G Protein-Coupled Receptors in Drug Delivery, eds Wayne R Leifert, Humana Press, USA, pp. 97-113.

Karczmar, A.G., Lindstrom, J., Christopoulos, A., 2007, History of research on nicotinic and muscarinic cholinergic receptors, in Exploring the Vertebrate Central Cholinergic Nervous System, eds Alexander G Karczmar, Springer Science+Business Media, New York USA, pp. 151-162.

Christopoulos, A., 2007, Muscarinic acetylcholine receptors in the central nervous system: structure, function and pharmacology, in Exploring the Vertebrate Central Cholinergic Nervous System, eds Alexander G Karczmar, Springer Science+Business Media, New York USA, pp. 163-208.

Journal Articles

Laskaris, L., Di Biase, M.A., Everall, I.P., Chana, G., Christopoulos, A., Skafidas, E.S., Cropley, V.L., Pantelis, C., 2016, Microglial activation and progressive brain changes in schizophrenia, British Journal of Pharmacology [P], vol 173, issue 4, Wiley-Blackwell, Hoboken NJ USA, pp. 666-680.

Imlach, W.L., Bhola, R.F., May, L.T., Christopoulos, A., Christie, M.J., 2015, A positive allosteric modulator of the adenosine A1 receptor selectively inhibits primary afferent synaptic transmission in a neuropathic pain model, Molecular Pharmacology [P], vol 88, issue 3, American Society for Pharmacology and Experimental Therapeutics, Bethesda MD USA, pp. 460-468.

Szabo, M., Huynh, T., Valant, C., Lane, J.R.D., Sexton, P., Christopoulos, A., Capuano, B., 2015, A structure-activity relationship study of the positive allosteric modulator LY2033298 at the M4 muscarinic acetylcholine receptor, MedChemComm [P], vol 6, issue 11, RSC Publishing, Cambridge UK, pp. 1998-2003.

Khajehali, E., Malone, D.T., Glass, M., Sexton, P., Christopoulos, A., Leach, K., 2015, Biased agonism and biased allosteric modulation at the CB1 cannabinoid receptors, Molecular Pharmacology [P], vol 88, issue 2, American Society for Pharmacology and Experimental Therapeutics, Bethesda MD USA, pp. 368-379.

Thompson, G.L., Lane, J.R.D., Coudrat, T., Sexton, P., Christopoulos, A., Canals, M., 2015, Biased agonism of endogenous opioid peptides at the mu-opioid receptor, Molecular Pharmacology [P], vol 88, issue 2, American Society for Pharmacology and Experimental Therapeutics, Bethesda MD USA, pp. 335-346.

Cook, A.E., Mistry, S.N., Gregory, K.J., Furness, S.G.B., Sexton, P., Scammells, P.J., Conigrave, A., Christopoulos, A., Leach, K., 2015, Biased allosteric modulation at the CaS receptor engendered by structurally diverse calcimimetics, British Journal of Pharmacology [P], vol 172, issue 1, John Wiley & Sons, Chichester West Sussex UK, pp. 185-200.

Chen, N., Malone, D.T., Pabreja, K., Sexton, P., Christopoulos, A., Canals, M., 2015, Detection and quantification of allosteric modulation of endogenous M4 muscarinic acetylcholine receptor using impedance-based label-free technology in a neuronal cell line, Journal of Biomolecular Screening [P], vol 20, issue 5, SAGE Publications Ltd, Thousand Oaks CA USA, pp. 646-654.

Dong, M., Vattelana, A.M., Lam, P.C.H., Orry, A., Abagyan, R., Christopoulos, A., Sexton, P., Haines, D.R., Miller, L.J., 2015, Development of a highly selective allosteric antagonist radioligand for the type 1 cholecystokinin receptor and elucidation of its molecular basis of binding, Molecular Pharmacology [P], vol 87, issue 1, American Society for Pharmacology and Experimental Therapeutics, Bethesda MD USA, pp. 130-140.

Koole, C.R., Wootten, D.L., Simms, J.W., Miller, L.J., Christopoulos, A., Sexton, P., 2015, Differential impact of amino acid substitutions on critical residues of the human glucagon-like peptide-1 receptor involved in peptide activity and small-molecule allosterys, Journal Of Pharmacology And Experimental Therapeutics [P], vol 353, issue 1, American Society for Pharmacology and Experimental Therapeutics, Bethesda MD USA, pp. 52-63.

Mistry, S.N., Shonberg, J., Draper-Joyce, C.J., Klein Herenbrink, C., Michino, M., Shi, L., Christopoulos, A., Capuano, B., Scammells, P.J., Lane, J.R.D., 2015, Discovery of a novel class of negative allosteric modulator of the dopamine D2 receptor through fragmentation of a bitopic ligand, Journal of Medicinal Chemistry [P], vol 58, issue 17, ACS Publications, Washington DC USA, pp. 6819-6843.

Burford, N.T., Livingston, K.E., Canals, M., Ryan, M.R., Budenholzer, L.M.L., Han, Y., Shang, Y., Herbst, J.J., O'Connell, J., Banks, M., Zhang, L., Filizola, M., Bassoni, D.L., Wehrman, T.S., Christopoulos, A., Traynor, J.R., Gerritz, S.W., Alt, A., 2015, Discovery, synthesis, and molecular pharmacology of selective positive allosteric modulators of the delta-opioid receptor, Journal of Medicinal Chemistry [P], vol 58, issue 10, ACS Publications, Washington DC USA, pp. 4220-4229.

Van Der Westhuizen, E.T., Valant, C., Sexton, P., Christopoulos, A., 2015, Endogenous allosteric modulators of G protein-coupled receptors, Journal of Pharmacology and Experimental Therapeutics [E], vol 353, issue 2, American Society for Pharmacology and Experimental Therapeutics, Bethesda MD USA, pp. 246-260.

Riddy, D.M., Valant, C., Rueda, P., Charman, W.N., Sexton, P., Summers, R.J., Christopoulos, A., Langmead, C.J., 2015, Label-free kinetics: exploiting functional hemi-equilibrium to derive rate constants for muscarinic receptor antagonists, Molecular Pharmacology [P], vol 88, issue 4, American Society for Pharmacology and Experimental Therapeutics, Bethesda MD USA, pp. 779-790.

Desai, A.J., Lam, P.C.H., Orry, A., Abagyan, R., Christopoulos, A., Sexton, P., Miller, L.J., 2015, Molecular mechanism of action of triazolobenzodiazepinone agonists of the type 1 cholecystokinin receptor. Possible cooperativity across the receptor homodimeric complex, Journal of Medicinal Chemistry [P], vol 58, issue 24, ACS Publications, Washington DC USA, pp. 9562-9577.

Thompson, G.L., Kelly, E., Christopoulos, A., Canals, M., 2015, Novel GPCR paradigms at the mu-opioid receptor, British Journal of Pharmacology [P], vol 172, issue 2, Wiley-Blackwell, Hoboken NJ USA, pp. 287-296.

Gentry, P., Sexton, P., Christopoulos, A., 2015, Novel allosteric modulators of G protein-coupled receptors, Journal Of Biological Chemistry [P], vol 290, issue 32, American Society for Biochemistry and Molecular Biology Inc, Bethesda MD USA, pp. 19478-19488.

Szabo, M., Lim, H.D., Klein Herenbrink, C., Christopoulos, A., Lane, J.R.D., Capuano, B., 2015, Proof of concept study for designed multiple ligands targeting the dopamine D2, serotonin 5-HT2A, and muscarinic M1 acetylcholine receptors, Journal of Medicinal Chemistry [P], vol 58, issue 3, ACS Publications, Washington DC USA, pp. 1550-1555.

Brennan, S.C., Mun, H., Leach, K., Kuchel, P.W., Christopoulos, A., Conigrave, A., 2015, Receptor expression modulates calcium-sensing receptor mediated intracellular Ca2+ mobilization, Endocrinology [P], vol 156, issue 4, The Endocrine Society, Chevy Chase MD USA, pp. 1330-1342.

Shonberg, J., Draper-Joyce, C.J., Mistry, S.N., Christopoulos, A., Scammells, P.J., Lane, J.R.D., Capuano, B., 2015, Structure-activity study of N-((trans)-4-(2-(7-cyano-3,4-dihydroisoquinolin-2(1H)-yl)ethyl)cyclohexyl)-1H-indole-2-carboxamide (SB269652), a bitopic ligand that acts as a negative allosteric modulator of the dopamine D2 receptor, Journal of Medicinal Chemistry [P], vol 58, issue 13, ACS Publications, Washington DC USA, pp. 5287-5307.

Huynh, T., Valant, C., Crosby, I.T., Sexton, P., Christopoulos, A., Capuano, B., 2015, Synthesis and pharmacological evaluation of M4 muscarinic receptor positive allosteric modulators derived from VU10004, ACS Chemical Neuroscience [E], vol 6, issue 6, ACS Publications, Washington DC USA, pp. 838-844.

Leach, K., Conigrave, A., Sexton, P., Christopoulos, A., 2015, Towards tissue-specific pharmacology: insights from the calcium-sensing receptor as a paradigm for GPCR (patho)physiological bias, Trends in Pharmacological Sciences [P], vol 36, issue 4, Elsevier, Kidlington Oxford UK, pp. 215-225.

Lane, J.R.D., Donthamsetti, P., Shonberg, J., Draper-Joyce, C.J., Dentry, S., Michino, M., Shi, L., Lopez Munoz, L., Scammells, P.J., Capuano, B., Sexton, P., Javitch, J.A., Christopoulos, A., 2014, A new mechanism of allostery in a G protein-coupled receptor dimer, Nature Chemical Biology [P], vol 10, issue 9, Nature Publishing Group, London UK, pp. 745-752.

Christopoulos, A., 2014, Advances in G protein-coupled receptor allostery: From function to structure, Molecular Pharmacology [P], vol 86, issue 5, American Society for Pharmacology and Experimental Therapeutics, Bethesda MD USA, pp. 463-478.

Yeatman, H.R., Lane, J.R.D., Choy, K.H.C., Lambert, N., Sexton, P., Christopoulos, A., Canals, M., 2014, Allosteric modulation of M1 muscarinic acetylcholine receptor internalization and subcellular trafficking, Journal Of Biological Chemistry [P], vol 289, issue 22, American Society for Biochemistry and Molecular Biology, Bethesda MD USA, pp. 15856-15866.

De Smet, F., Christopoulos, A., Carmeliet, P., 2014, Allosteric targeting of receptor tyrosine kinases, Nature Biotechnology [P], vol 32, issue 11, Nature Publishing Group, New York NY USA, pp. 1113-1120.

Shonberg, J., Lopez Munoz, L., Scammells, P.J., Christopoulos, A., Capuano, B., Lane, J.R.D., 2014, Biased agonism at G protein-coupled receptors: The promise and the challenges - A medicinal chemistry perspective, Medicinal Research Reviews [P], vol 34, issue 6, John Wiley & Sons, Inc., Hoboken NJ USA, pp. 1286-1330.

Croy, C.H., Schober, D.A., Xiao, H., Quets, A., Christopoulos, A., Felder, C.C., 2014, Characterization of the novel positive allosteric modulator, LY2119620, at the muscarinic M(2) and M(4) receptors, Molecular Pharmacology [E], vol 86, issue 1, American Society for Pharmacology and Experimental Therapeutics, Bethesda MD USA, pp. 106-115.

Davie, B.J., Sexton, P., Capuano, B., Christopoulos, A., Scammells, P.J., 2014, Development of a photoactivatable allosteric ligand for the M1 muscarinic acetylcholine receptor, ACS Chemical Neuroscience [E], vol 5, issue 10, American Chemical Society, Washington DC USA, pp. 902-907.

Schober, D.A., Croy, C.H., Xiao, H., Christopoulos, A., Felder, C.C., 2014, Development of a radioligand, [(3)H]LY2119620, to probe the human M(2) and M(4) muscarinic receptor allosteric binding sites, Molecular Pharmacology [P], vol 86, issue 1, American Society for Pharmacology and Experimental Therapeutics, Bethesda MD USA, pp. 116-123.

Leach, K., Sexton, P., Christopoulos, A., Conigrave, A., 2014, Engendering biased signalling from the calcium-sensing receptor for the pharmacotherapy of diverse disorders, British Journal of Pharmacology [P], vol 171, issue 5, John Wiley & Sons Ltd, Chichester UK, pp. 1142-1155.

Langmead, C.J., Christopoulos, A., 2014, Functional and structural perspectives on allosteric modulation of GPCRs, Current Opinion in Cell Biology [P], vol 27, issue 1, Elsevier Ltd, Oxford UK, pp. 94-101.

Christopoulos, A., Changeux, J., Catterall, W.A., Fabbro, D., Burris, T.P., Cidlowski, J.A., Olsen, R.W., Peters, J.A., Neubig, R., Pin, J., Sexton, P., Kenakin, T.P., Ehlert, F.J., Spedding, M., Langmead, C.J., 2014, International union of basic and clinical pharmacology. XC. Multisite pharmacology: Recommendations for the nomenclature of receptor allosterism and allosteric ligands, Pharmacological Reviews [P], vol 66, issue 4, American Society for Pharmacology and Experimental Therapeutics, Bethesda MD USA, pp. 918-947.

Abdul Ridha, A., Lane, J.R.D., Mistry, S.N., Lopez Munoz, L., Sexton, P., Scammells, P.J., Christopoulos, A., Canals, M., 2014, Mechanistic insights into allosteric structure-function relationships at the M1 muscarinic acetylcholine receptor, Journal Of Biological Chemistry [P], vol 289, issue 48, American Society for Biochemistry and Molecular Biology Inc., Bethesda MD USA, pp. 33701-33711.

Abdul Ridha, A., Lopez, L., Keov, P., Thal, D., Mistry, S.N., Sexton, P., Lane, J.R.D., Canals, M., Christopoulos, A., 2014, Molecular determinants of allosteric modulation at the M1 muscarinic acetylcholine receptor, Journal Of Biological Chemistry [P], vol 289, issue 9, American Society for Biochemistry and Molecular Biology Inc., Bethesda MD USA, pp. 6067-6079.

Keov, P., Lopez, L., Devine, S., Valant, C., Lane, J.R.D., Scammells, P.J., Sexton, P., Christopoulos, A., 2014, Molecular mechanisms of bitopic ligand engagement with the M1 muscarinic acetylcholine receptor, Journal Of Biological Chemistry [P], vol 289, issue 34, American Society for Biochemistry and Molecular Biology Inc., Bethesda MD USA, pp. 23817-23837.

Kruse, A.C., Kobilka, B., Gautam, D., Sexton, P.M., Christopoulos, A., Wess, J., 2014, Muscarinic acetylcholine receptors: Novel opportunities for drug development, Nature Reviews Drug Discovery [P], vol 13, issue 7, Nature Publishing Group (NPG), London UK, pp. 549-560.

Andreassen, K.V., Hjuler, S.T., Furness, S.G.B., Sexton, P.M., Christopoulos, A., Nosjean, O., Karsdal, M.A., Henriksen, K., 2014, Prolonged calcitonin receptor signaling by salmon, but not human calcitonin, reveals ligand bias, PLoS ONE [E], vol 9, issue 3 (Art. No: e92042), Public Library of Science, San Francisco CA USA, pp. 1-10.

van der Westhuizen, E.T., Breton, B., Christopoulos, A., Bouvier, M., 2014, Quantification of ligand bias for clinically relevant beta2-adrenergic receptor ligands: Implications for drug taxonomy, Molecular Pharmacology [P], vol 85, issue 3, American Society for Pharmacology and Experimental Therapeutics, Bethesda MD USA, pp. 492-509.

Goolam, M.A., Ward, J.H., Avlani, V.A., Leach, K., Christopoulos, A., Conigrave, A., 2014, Roles of intraloops-2 and -3 and the proximal C-terminus in signalling pathway selection from the human calcium-sensing receptor, FEBS Letters [P], vol 588, issue 18, Elsevier BV, Amsterdam Netherlands, pp. 3340-3346.

Valant, C., May, L.T., Aurelio, L., Chuo, C.H., White, P.J., Baltos, J., Sexton, P., Scammells, P.J., Christopoulos, A., 2014, Separation of on-target efficacy from adverse effects through rational design of a bitopic adenosine receptor agonist, Proceedings Of The National Academy Of Sciences Of The United States Of America [P], vol 111, issue 12, National Academy of Sciences, Washington DC USA, pp. 4614-4619.

Millard, C.J., Ludeman, J.P., Canals, M., Bridgford, J.L., Hinds, M.G., Clayton, D.J., Christopoulos, A., Payne, R.J., Stone, M.J., 2014, Structural basis of receptor sulfotyrosine recognition by a CC chemokine: the N-terminal region of CCR3 bound to CCL11/eotaxin-1, Structure [P], vol 22, issue 11, Cell Press, United States, pp. 1571-1581.

Szabo, M., Klein Herenbrink, C., Christopoulos, A., Lane, J.R.D., Capuano, B., 2014, Structure-activity relationships of privileged structures lead to the discovery of novel biased ligands at the dopamine D2 receptor, Journal of Medicinal Chemistry [P], vol 57, issue 11, American Chemical Society, Washington DC USA, pp. 4924-4939.

Davie, B.J., Valant, C., White, J., Sexton, P., Capuano, B., Christopoulos, A., Scammells, P.J., 2014, Synthesis and pharmacological evaluation of analogues of benzyl quinolone carboxylic acid (BQCA) designed to bind irreversibly to an allosteric site of the M1 muscarinic acetylcholine receptor, Journal of Medicinal Chemistry [P], vol 57, issue 12, American Chemical Society, Washington DC USA, pp. 5405-5418.

Savage, E.E., Wootten, D.L., Christopoulos, A., Sexton, P., Furness, S.G.B., 2013, A simple method to generate stable cell lines for the analysis of transient protein-protein interactions, BioTechniques [P], vol 54, issue 4, Informa Healthcare USA, United States, pp. 217-221.

Shonberg, J., Klein Herenbrink, C., Lopez, L., Christopoulos, A., Scammells, P.J., Capuano, B., Lane, J.R.D., 2013, A structure-activity analysis of biased agonism at the dopamine D2 receptor, Journal of Medicinal Chemistry [P], vol 56, issue 22, ACS Publications, Washington DC USA, pp. 9199-9221.

Kruse, A.C., Ring, A.M., Manglik, A., Hu, J., Hu, K., Eitel, K., Hubner, H., Pardon, E., Valant, C., Sexton, P., Christopoulos, A., Felder, C.C., Gmeiner, P., Steyaert, J., Weis, W., Garcia, K.C., Wess, J., Kobilka, B., 2013, Activation and allosteric modulation of a muscarinic acetylcholine receptor, Nature [P], vol 504, issue 7478, Nature Publishing Group (NPG), London UK, pp. 101-106.

Abdul Ridha, A., Lane, J.R.D., Sexton, P., Canals, M., Christopoulos, A., 2013, Allosteric modulation of a chemogenetically modified G protein-coupled receptor, Molecular Pharmacology [P], vol 83, issue 2, American Society for Pharmacology and Experimental Therapeutics, USA, pp. 521-530.

Lane, J.R.D., Sexton, P.M., Christopoulos, A., 2013, Bridging the gap: bitopic ligands of G-protein-coupled receptors, Trends in Pharmacological Sciences [P], vol 34, issue 1, Elsevier, UK, pp. 59-66.

Avlani, V.A., Ma, W., Mun, H., Leach, K., Delbridge, L., Christopoulos, A., Conigrave, A., 2013, Calcium-sensing receptor-dependent activation of CREB phosphorylation in HEK293 cells and human parathyroid cells, American Journal of Physiology - Endocrinology and Metabolism [E], vol 304, issue 10, American Physiological Society, USA, pp. 1097-1104.

Davie, B.J., Christopoulos, A., Scammells, P.J., 2013, Development of M1 mAChR allosteric and bitopic ligands: Prospective therapeutics for the treatment of cognitive deficits, ACS Chemical Neuroscience [E], vol 4, issue 7, ACS Publications, Washington DC USA, pp. 1026-1048.

Wootten, D.L., Savage, E.E., Willard, F.S., Bueno, A.B., Sloop, K.W., Christopoulos, A., Sexton, P., 2013, Differential activation and modulation of the glucagon-like peptide-1 receptor by small molecule ligands, Molecular Pharmacology [P], vol 83, issue 4, American Society for Pharmacology and Experimental Therapeutics, USA, pp. 822-834.

Wootten, D.L., Christopoulos, A., Sexton, P., 2013, Emerging paradigms in GPCR allostery: implications for drug discovery, Nature Reviews Drug Discovery [P], vol 12, issue 8, Nature Publishing Group (NPG), UK, pp. 630-644.

Maher, A.R., Arif, S., Madhani, M., Abozguia, K., Ahmed, I., Fernandez, B.O., Feelisch, M., O'Sullivan, A.G., Christopoulos, A., Sverdlov, A.L., Ngo, D., Dautov, R., James, P.E., Horowitz, J.D., Frenneaux, M.P., 2013, Impact of chronic congestive heart failure on pharmacokinetics and vasomotor effects of infused nitrite, British Journal of Pharmacology [P], vol 169, issue 3, John Wiley & Sons, UK, pp. 659-670.

Leach, K., Wen, C., Cook, A.E., Sexton, P., Conigrave, A., Christopoulos, A., 2013, Impact of clinically relevant mutations on the pharmacoregulation and signaling bias of the calcium-sensing receptor by positive and negative allosteric modulators, Endocrinology [P], vol 154, issue 3, Endocrine Society, USA, pp. 1105-1116.

Bono, F., De Smet, F., Herbert, C., De Bock, K., Georgiadou, M., Fons, P., Tjwa, M., Alcouffe, C., Ny, A., Bianciotto, M., Jonckx, B., Murakami, M., Lanahan, A.A., Michielsen, C., Sibrac, D., Dol-Gleizes, F., Mazzone, M., Zacchigna, S., Herault, J., Fischer, C., Rigon, P., Ruiz de Almodovar, C., Claes, F., Blanc, I., Poesen, K., Zhang, Z., Segura, I., Gueguen, G., Bordes, M., Lambrechts, D., Broussy, R., van de Wouwer, M., Michaux, C., Shimada, T., Jean, I., Blacher, S., Noel, A., Motte, P., Rom, E., Rakic, J., Katsuma, S., Schaeffer, P., Yayon, A., Van Schepdael, A., Schwalbe, H., Gervasio, F.L., Carmeliet, G., Rozensky, J., Dewerchin, M., Simons, M., Christopoulos, A., Herbert, J., Carmeliet, P., 2013, Inhibition of tumor angiogenesis and growth by a small-molecule multi-FGF receptor blocker with allosteric properties, Cancer Cell [P], vol 23, issue 4, Cell Press, USA, pp. 477-488.

Kenakin, T., Christopoulos, A., 2013, Measurements of ligand bias and functional affinity, Nature Reviews Drug Discovery [P], vol 12, issue 6, Nature Publishing Group, UK, p. 483.

Koole, C.R., Savage, E.E., Christopoulos, A., Miller, L.J., Sexton, P., Wootten, D.L., 2013, Minireview: Signal bias, allosterism, and polymorphic variation at the GLP-1R: implications for drug discovery, Molecular Endocrinology [P], vol 27, issue 8, Endocrine Society, USA, pp. 1234-1244.

Harikumar, K.G., Cawston, E.E., Lam, P.C.H., Patil, A., Orry, A., Henke, B., Abagyan, R., Christopoulos, A., Sexton, P., Miller, L.J., 2013, Molecular basis for benzodiazepine agonist action at the type 1 cholecystokinin receptor, Journal Of Biological Chemistry [P], vol 288, issue 29, American Society for Biochemistry and Molecular Biology, USA, pp. 21082-21095.

Wootten, D.L., Simms, J.W., Miller, L.J., Christopoulos, A., Sexton, P., 2013, Polar transmembrane interactions drive formation of ligand-specific and signal pathway-biased family B G protein-coupled receptor conformations, Proceedings Of The National Academy Of Sciences Of The United States Of America [P], vol 110, issue 13, National Academies Press, USA, pp. 5211-5216.

Huynh, T., Valant, C., Crosby, I.T., Sexton, P., Christopoulos, A., Capuano, B., 2013, Probing structural requirements of positive allosteric modulators of the M4 muscarinic receptor, Journal of Medicinal Chemistry [P], vol 56, issue 20, ACS Publications, Washington DC USA, pp. 8196-8200.

Koole, C.R., Pabreja, K., Savage, E.E., Wootten, D.L., Furness, S.G.B., Miller, L.J., Christopoulos, A., Sexton, P., 2013, Recent advances in understanding GLP-1R (glucagon-like peptide-1 receptor) function, Biochemical Society Transactions [P], vol 41, issue 1, Portland Press, UK, pp. 172-179.

Keov, P., Valant, C., Devine, S., Lane, J.R., Scammells, P.J., Sexton, P., Christopoulos, A., 2013, Reverse engineering of the selective agonist TBPB unveils both orthosteric and allosteric modes of action at the M1 muscarinic acetylcholine receptor, Molecular Pharmacology [P], vol 84, issue 3, American Society for Pharmacology and Experimental Therapeutics, USA, pp. 425-437.

Kenakin, T., Christopoulos, A., 2013, Signalling bias in new drug discovery: detection, quantification and therapeutic impact, Nature Reviews Drug Discovery [P], vol 12, Nature Publishing Group (NPG), London UK, pp. 205-216.

Dror, R., Green, H.F., Valant, C., Borhani, D.W., Valcourt, J.R., Pan, A.C., Arlow, D.H., Canals, M., Lane, J.R.D., Rahmani, R.S., Baell, J.B., Sexton, P., Christopoulos, A., Shaw, D.E., 2013, Structural basis for modulation of a G-protein-coupled receptor by allosteric drugs, Nature [P], vol 503, issue 7475, Nature Publishing Group (NPG), London UK, pp. 295-299.

Langmead, C.J., Christopoulos, A., 2013, Supra-physiological efficacy at GPCRs: superstition or super agonists?, British Journal of Pharmacology [P], vol 169, issue 2, John Wiley & Sons, UK, pp. 353-356.

Mistry, S.N., Valant, C., Sexton, P., Capuano, B., Christopoulos, A., Scammells, P.J., 2013, Synthesis and pharmacological profiling of analogues of benzyl quinolone carboxylic acid (BQCA) as allosteric modulators of the M{1} muscarinic receptor, Journal of Medicinal Chemistry [P], vol 56, issue 12, ACS Publications, USA, pp. 5151-5172.

Tan Hoong Yu, J., Ludeman, J.P., Wedderburn, J., Canals, M., Hall, P.H., Butler, S.J., Taleski, D., Christopoulos, A., Hickey, M.J., Payne, R.J., Stone, M.J., 2013, Tyrosine sulfation of chemokine receptor CCR2 enhances interactions with both monomeric and dimeric forms of the chemokine monocyte chemoattractant protein-1 (MCP-1), Journal Of Biological Chemistry [P], vol 288, issue 14, American Society for Biochemistry and Molecular Biology, USA, pp. 10024-10034.

Canals, M., Lane, J., Wen, A., Scammells, P., Sexton, P., Christopoulos, A., 2012, A Monod-Wyman-Changeux mechanism can explain G protein-coupled receptor (GPCR) allosteric modulation, Journal Of Biological Chemistry [P], vol 287, issue 1, American Society for Biochemistry and Molecular Biology, United States, pp. 650-659.

Kenakin, T., Watson, C., Muniz-Medina, V., Christopoulos, A., Novick, S., 2012, A simple method for quantifying functional selectivity and agonist bias, ACS Chemical Neuroscience [E], vol 3, issue 3, ACS Publications, USA, pp. 193-203.

Wootten, D.L., Savage, E.E., Valant, C., May, L.T., Sloop, K.W., Ficorilli, J., Showalter, A.D., Willard, F.S., Christopoulos, A., Sexton, P.M., 2012, Allosteric modulation of endogenous metabolites as an avenue for drug discovery, Molecular Pharmacology [P], vol 82, issue 2, American Society for Pharmacology and Experimental Therapeutics, USA, pp. 281-290.

Melancon, B.J., Hopkins, C.R., Wood, M.R., Emmitte, K.A., Niswender, C.M., Christopoulos, A., Conn, P.J., Lindsley, C.W., 2012, Allosteric modulation of seven transmembrane spanning receptors: theory, practice, and opportunities for central nervous system drug discovery, Journal of Medicinal Chemistry [P], vol 55, issue 4, ACS Publications, USA, pp. 1445-1464.

Furness, S.G.B., Wootten, D.L., Christopoulos, A., Sexton, P.M., 2012, Consequences of splice variation on secretin family G protein-coupled receptor function, British Journal of Pharmacology [P], vol 166, issue 1, Wiley-Blackwell, Malden USA, pp. 98-109.

Tan Hoong Yu, J., Canals, M., Ludeman, J.P., Wedderburn, J., Boston, C., Butler, S.J., Carrick, A.M., Parody, T.R., Taleski, D., Christopoulos, A., Payne, R.J., Stone, M.J., 2012, Design and receptor interactions of obligate dimeric mutant of chemokine monocyte chemoattractant protein-1 (MCP-1), Journal Of Biological Chemistry [P], vol 287, issue 18, American Society for Biochemistry and Molecular Biology, USA, pp. 14692-14702.

Harikumar, K.G., Wootten, D.L., Pinon, D.I., Koole, C.R., Ball, A.M., Furness, S.G., Graham, B., Dong, M., Christopoulos, A., Miller, L.J., Sexton, P.M., 2012, Glucagon-like peptide-1 receptor dimerization differentially regulates agonist signaling but does not affect small molecule allostery, Proceedings Of The National Academy Of Sciences Of The United States Of America [P], vol 109, issue 45, National Academies Press, USA, pp. 18607-18612.

Leach, K., Wen, C., Davey, A.E., Sexton, P.M., Conigrave, A.D., Christopoulos, A., 2012, Identification of molecular phenotypes and biased signaling induced by naturally occurring mutations of the human calcium-sensing receptor, Endocrinology [P], vol 153, issue 9, Endocrine Society, USA, pp. 4304-4316.

Davey, A.E., Leach, K., Valant, C., Conigrave, A.D., Sexton, P.M., Christopoulos, A., 2012, Positive and negative allosteric modulators promote biased signaling at the calcium-sensing receptor, Endocrinology [P], vol 153, issue 3, Endocrine Society, USA, pp. 1232-1241.

Valant, C., Felder, C.C., Sexton, P.M., Christopoulos, A., 2012, Probe dependence in the allosteric modulation of a G protein-coupled receptor: implications for detection and validation of allosteric ligand effects, Molecular Pharmacology [P], vol 81, issue 1, American Society for Pharmacology and Experimental Therapeutics, USA, pp. 41-52.

Koole, C.R., Wootten, D.L., Simms, J., Savage, E.E., Miller, L.J., Christopoulos, A., Sexton, P.M., 2012, Second extracellular loop of human glucagon-like peptide-1 receptor (GLP-1R) differentially regulates orthosteric but not allosteric agonist binding and function, Journal Of Biological Chemistry [P], vol 287, issue 6, American Society for Biochemistry and Molecular Biology, Bethesda USA, pp. 3659-3673.

Koole, C.R., Wootten, D.L., Simms, J.W., Miller, L.J., Christopoulos, A., Sexton, P., 2012, Second extracellular loop of human glucagon-like peptide-1 receptor (GLP-1R) has a critical role in GLP-1 peptide binding and receptor activation, Journal Of Biological Chemistry [P], vol 287, issue 6, American Society for Biochemistry and Molecular Biology, Bethesda USA, pp. 3642-3658.

Willard, F.S., Wootten, D.L., Showalter, A.D., Savage, E.E., Ficorilli, J., Farb, T.B., Bokvist, K., Alsina-Fernandez, J., Furness, S.G., Christopoulos, A., Sexton, P.M., Sloop, K.W., 2012, Small molecule allosteric modulation of the glucagon-like Peptide-1 receptor enhances the insulinotropic effect of oxyntomodulin, Molecular Pharmacology [P], vol 82, issue 6, American Society for Pharmacology and Experimental Therapeutics, USA, pp. 1066-1073.

Gregory, K.J., Sexton, P.M., Tobin, A.B., Christopoulos, A., 2012, Stimulus bias provides evidence for conformational constraints in the structure of a G protein-coupled receptor, Journal Of Biological Chemistry [P], vol 287, issue 44, American Society for Biochemistry and Molecular Biology, USA, pp. 37066-37077.

Conway, R., Valant, C., Christopoulos, A., Robertson, A.D., Capuano, B., Crosby, I.T., 2012, Synthesis and SAR study of 4-arylpiperidines and 4-aryl-1,2,3,6- tetrahydropyridines as 5-HT2C agonists, Bioorganic & Medicinal Chemistry Letters [P], vol 22, issue 7, Pergamon, UK, pp. 2560-2564.

Valant, C., Aurelio, L., Devine, S.M., Ashton, T.D., White, J.M., Sexton, P.M., Christopoulos, A., Scammells, P.J., 2012, Synthesis and characterization of novel 2-amino-3-benzoylthiophene derivatives as biased allosteric agonists and modulators of the adenosine A1 receptor, Journal of Medicinal Chemistry [P], vol 55, issue 5, ACS Publications, USA, pp. 2367-2375.

Valant, C., Lane, J., Sexton, P., Christopoulos, A., 2012, The best of both worlds? Bitopic orthosteric/allosteric ligands of G protein - coupled receptors, Annual Review Of Pharmacology And Toxicology [P], vol 53, Annual Reviews, United States, pp. 153-178.

Keov, P., Sexton, P., Christopoulos, A., 2011, Allosteric modulation of G protein-coupled receptors: A pharmacological perspective, Neuropharmacology [P], vol 60, issue 1, Pergamon Press, Oxford UK, pp. 24-35.

Broadhead, G., Mun, H., Avlani, V., Jourdon, O., Church, W., Christopoulos, A., Delbridge, L., Conigrave, A., 2011, Allosteric modulation of the calcium-sensing receptor by gamma-glutamyl peptides inhibition of PTH secretion, suppression of intraceullar cAMP levels and a common mechanism of action with L-amino acids, Journal Of Biological Chemistry [P], vol 286, issue 11, American Society for Biochemistry and Molecular Biology, USA, pp. 8786-8797.

Canals, M., Sexton, P., Christopoulos, A., 2011, Allostery in GPCRs: 'MWC' revisited, Trends In Biochemical Sciences [P], vol 36, issue 12, Elsevier, UK, pp. 663-672.

Kenakin, T., Christopoulos, A., 2011, Analytical pharmacology: the impact of numbers on pharmacology, Trends in Pharmacological Sciences [P], vol 32, issue 4, Elsevier, UK, pp. 189-196.

Suratman, N.S., Leach, K., Sexton, P., Felder, C.C., Loiacono, R., Christopoulos, A., 2011, Impact of species variability and "probe-dependence" on the detection and in vivo validation of allosteric modulation at the M(4) muscarinic acetylcholine receptor, British Journal of Pharmacology [P], vol 162, issue 7, John Wiley & Sons, UK, pp. 1659-1670.

Stallaert, W., Christopoulos, A., Bouvier, M., 2011, Ligand functional selectivity and quantitative pharmacology at G protein-coupled receptors, Expert Opinion on Drug Discovery [P], vol 6, issue 8, Informa Healthcare USA, UK, pp. 811-825.

Wootten, D., Simms, J., Koole, C., Woodman, O., Summers, R., Christopoulos, A., Sexton, P., 2011, Modulation of the glucagon-like peptide-1 receptor signaling by naturally occurring and synthetic flavonoids, Journal Of Pharmacology And Experimental Therapeutics [P], vol 336, issue 2, Lippincott Williams & Wilkins, AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS, pp. 540-550.

Koole, C., Wootten, D., Simms, J., Valant, C., Miller, L., Christopoulos, A., Sexton, P., 2011, Polymorphism and ligand dependent changes in human glucagon-like peptide-1 receptor (GLP-1R) function: allosteric rescue of loss of function mutation, Molecular Pharmacology [P], vol 80, issue 3, American Society for Pharmacology and Experimental Therapeutics, USA, pp. 486-497.

Leach, K., Sexton, P., Christopoulos, A., 2011, Quantification of allosteric interactions at G protein-coupled receptors using radioligand binding assays, Current Protocols in Pharmacology [P], vol 1, issue Supp 52 (Unit 1.22), John Wiley & Sons, USA, pp. 1-41.

Evans, B.A., Broxton, N., Merlin, J., Sato, M., Hutchinson, D.S., Christopoulos, A., Summers, R.J., 2011, Quantification of functional selectivity at the human {alpha}1A-adrenoceptor, Molecular Pharmacology [P], vol 79, issue 2, American Society for Pharmacology and Experimental Therapeutics, USA, pp. 298-307.

Bosnyak, S., Jones, E., Christopoulos, A., Aguilar, M., Thomas, W., Widdop, R., 2011, Relative affinity of angiotensin peptides and novel ligands at AT1 and AT2 receptors, Clinical Science [P], vol 121, issue 7, Portland Press, UK, pp. 297-303.

Leach, K., Davey, A.E., Felder, C.C., Sexton, P., Christopoulos, A., 2011, The role of transmembrane domain 3 (Tmiii) in the actions of orthosteric, allosteric and atypical agonists of the M4 muscarinic acetylcholine receptor, Molecular Pharmacology [P], vol 79, issue 5, American Society for Pharmacology and Experimental Therapeutics, USA, pp. 855-865.

Aurelio, L., Christopoulos, A., Flynn, B., Scammells, P., Sexton, P., Valant, C., 2011, The synthesis and biological evaluation of 2-amino-4,5,6,7,8,9-hexahydrocycloocta[b]thiophenes as allosteric modulators of the A(1) adenosine receptor, Bioorganic & Medicinal Chemistry Letters [P], vol 21, issue 12, Pergamon-Elsevier, UK, pp. 3704-3707.

Koole, C., Wootten, D., Simms, J., Valant, C., Sridhar, R., Woodman, O., Miller, L., Summers, R., Christopoulos, A., Sexton, P.M., 2010, Allosteric ligands of the glucagon-like peptide 1 receptor (GLP-1R) differentially modulate endogenous and exogenous peptide responses in a pathway-selective manner: Implications for drug screening, Molecular Pharmacology [P], vol 78, issue 3, American Society for Pharmacology and Experimental Therapeutics, USA, pp. 456-465.

Valant, C., Aurelio, L., Urmaliya, V., White, P., Scammells, P., Sexton, P., Christopoulos, A., 2010, Delineating the mode of action of adenosine A1 receptor allosteric modulators, Molecular Pharmacology [P], vol 78, issue 3, American Society for Pharmacology and Experimental Therapeutics, United States, pp. 444-455.

Stewart, G.D., Sexton, P., Christopoulos, A., 2010, Detection of novel functional selectivity at M3 muscarinic acetylcholine receptors using a Saccharomyces cerevisiae platform, Acs Chemical Biology [P], vol 5, issue 4, ACS Publications, USA, pp. 365-375.

Aurelio, L., Valant, C., Flynn, B., Sexton, P., White, J., Christopoulos, A., Scammells, P., 2010, Effects of conformational restriction of 2-amino-3-benzoylthiophenes on A1 adenosine receptor modulation, Journal of Medicinal Chemistry [P], vol 53, ACS Publications, United States, pp. 6550-6559.

van der Westhuizen, E.T., Christopoulos, A., Sexton, P., Wade, J., Summers, R., 2010, H2 relaxin is a biased ligand relative to H3 relaxin at the relaxin family peptide receptor 3 (RXFP3) [S], Molecular Pharmacology [P], vol 77, issue 5, American Society for Pharmacology and Experimental Therapeutics, United States, pp. 759-772.

Gregory, K.J., Hall, N., Tobin, A., Sexton, P., Christopoulos, A., 2010, Identification of orthosteric and allosteric site mutations in M 2 muscarinic acetylcholine receptors that contribute to ligand-selective signaling bias, Journal Of Biological Chemistry [P], vol 285, issue 10, American Society for Biochemistry and Molecular Biology, USA, pp. 7459-7474.

Leach, K., Loiacono, R.E., Felder, C.C., McKinzie, D.L., Mogg, A., Shaw, D.B., Sexton, P.M., Christopoulos, A., 2010, Molecular mechanisms of action and in vivo validation of an M4 muscarinic acetylcholine receptor allosteric modulator with potential antipsychotic properties, Neuropsychopharmacology [P], vol 35, issue 4, Nature Publishing Group (NPG), UK & USA, pp. 855-869.

Avlani, V.A., Langmead, C.J., Guida, E., Wood, M.D., Tehan, B.G., Herdon, H.J., Watson, J.M., Sexton, P., Christopoulos, A., 2010, Orthosteric and allosteric modes of interaction of novel selective agonists of the M1 muscarinic acetylcholine receptor, Molecular Pharmacology [P], vol 78, issue 1, American Society for Pharmacology and Experimental Therapeutics, USA, pp. 94-104.

Gregory, K., Sexton, P., Christopoulos, A., 2010, Overview of receptor allosterism, Current Protocols in Pharmacology [P], vol Chapter 1, issue Supp 51, John Wiley & Sons, USA, pp. 1.21-1-1.21-34.

Stewart, G.D., Sexton, P., Christopoulos, A., 2010, Prediction of functionally selective allosteric interactions at an M 3 muscarinic acetylcholine receptor mutant using Saccharomyces cerevisiae, Molecular Pharmacology [P], vol 78, issue 2, American Society for Pharmacology and Experimental Therapeutics, USA, pp. 205-214.

Nawaratne, V., Leach, K., Felder, C.C., Sexton, P.M., Christopoulos, A., 2010, Structural determinants of allosteric agonism and modulation at the M 4 muscarinic acetylcholine receptor: Identification of ligand-specific and global activation mechanisms, Journal Of Biological Chemistry [P], vol 285, issue 25, American Society for Biochemistry and Molecular Biology, USA, pp. 19012-19021.

Robinson, S.A., Loiacono, R., Christopoulos, A., Sexton, P., Malone, D.T., 2010, The effect of social isolation on rat brain expression of genes associated with endocannabinoid signaling, Brain Research [P], vol 1343, Elsevier, The Netherlands, pp. 153-167.

Aurelio, L., Valant, C., Figler, H., Flynn, B.L., Linden, J., Sexton, P., Christopoulos, A., Scammells, P.J., 2009, 3- and 6-substituted 2-amino-4,5,6,7-tetrahydrothieno[2,3-c]pyridines as A1 adenosine receptor allosteric modulators and antagonists, Bioorganic & Medicinal Chemistry [P], vol 17, issue 20, Pergamon, UK, pp. 7353-7361.

Conn, P.J., Christopoulos, A., Lindsley, C.W., 2009, Allosteric modulators of GPCRs: a novel approach for the treatment of CNS disorders, Nature Reviews, Drug Discovery, vol 8, issue 1, Nature Publishing Group (NPG), UK, pp. 41-54.

Aurelio, L., Valant, C., Flynn, B.L., Sexton, P.M., Christopoulos, A., Scammells, P.J., 2009, Allosteric modulators of the adenosine A1 receptor: Synthesis and pharmacological evaluation of 4-substituted 2-amino-3-benzoylthiophenes, Journal of Medicinal Chemistry [P], vol 52, issue 14, ACS Publications, USA, pp. 4543-4547.

Mansfield, K.J., Chandran, J.J., Vaux, K.J., Millard, R.J., Christopoulos, A., Mitchelson, F.J., Burcher, E., 2009, Comparison of receptor binding characteristics of commonly used muscarinic antagonists in human bladder detrusor and mucosa, Journal of Pharmacology and Experimental Therapeutics, vol 328, American Society for Pharmacology and Experimental Therapeutics, United States, pp. 893-899.

Stewart, G.D., Valant, C., Dowell, S.J., Mijaljica, D., Devenish, R.J., Scammells, P.J., Sexton, P., Christopoulos, A., 2009, Determination of adenosine A1 receptor agonist and antagonist pharmacology using Saccharomyces cerevisiae: Implications for ligand screening and functional selectivity, Journal Of Pharmacology And Experimental Therapeutics [P], vol 331, issue 1, American Society for Pharmacology and Experimental Therapeutics, USA, pp. 277-286.

Antony, J., Kellershohn, K., Mohr-Andra, M., Kebig, A., Prilla, S., Muth, M., Heller, E., Disingrini, T., Dallanoce, C., Bertoni, S., Schrobang, J., Trankle, C., Kostenis, E., Christopoulos, A., Holtje, H., Barocelli, E., De Amici, M., Holzgrabe, U., Mohr, K., 2009, Dualsteric GPCR targeting: A novel route to binding and signaling pathway selectivity, The FASEB Journal, vol 23, Federation of American Societies for Experimental Biology, United States, pp. 442-450.

Lu, J.Y.L., Yang, Y., Gnacadja, G., Christopoulos, A., Reagan, J.D., 2009, Effect of the calcimimetic R-568 [3-(2-chlorophenyl)-N-((1R)-1-(3- methoxyphenyl)ethyl)-1-propanamine] on correcting inactivating mutations in the human calcium-sensing receptor, Journal Of Pharmacology And Experimental Therapeutics [P], vol 331, issue 3, American Society for Pharmacology and Experimental Therapeutics, USA, pp. 775-786.

Gao, F., Harikumar, K.G., Dong, M., Lam, P.C., Sexton, P.M., Christopoulos, A., Bordner, A., Abagyan, R., Miller, L.J., 2009, Functional importance of a structurally distinct homodimeric complex of the family B G protein-coupled secretin receptor, Molecular Pharmacology [P], vol 76, issue 2, American Society for Pharmacology and Experimental Therapeutics, USA, pp. 264-274.

Sexton, P.M., Poyner, D.R., Simms, J.W., Christopoulos, A., Hay, D.L., 2009, Modulating receptor function through RAMPs: can they represent drug targets in themselves?, Drug Discovery Today, vol 14, issue 7-8, Elsevier, UK, pp. 413-419.

Ferguson, G.N., Valant, C., Horne, H.J., Figler, H., Flynn, B.L., Linden, J., Chalmers, D.K., Sexton, P., Christopoulos, A., Scammells, P.J., 2008, 2-Aminothienopyridazines as novel adenosine A1 receptor allosteric modulators and antagonists, Journal of Medicinal Chemistry, vol 51, issue 19, ACS Publications, USA, pp. 6165-6172.

Valant, C., Gregory, K.J., Hall, N.E., Scammells, P.J., Lew, M., Sexton, P., Christopoulos, A., 2008, A novel mechanism of G protein-coupled receptor functional selectivity: Muscarinic partial agonist McN-A-343 as a bitopic orthosteric/allosteric ligand, Journal of Biological Chemistry, vol 283, issue 43, American Society for Biochemistry and Molecular Biology, United States, pp. 29312-29321.

Chan, W.Y., McKinzie, D.L., Bose, S., Mitchell, S.N., Witkin, J.M., Thompson, R.C., Christopoulos, A., Lazareno, S., Birdsall, N.J., Bymaster, F.P., Felder, C.C., 2008, Allosteric modulation of the muscarinic M4 receptor as an approach to treating schizophrenia, Proceedings of the National Academy of Sciences of the United States of America, vol 105, issue 31, National Academies Press, United States, pp. 10978-10983.

Gao, F., Sexton, P., Christopoulos, A., Miller, L.J., 2008, Benzodiazepine ligands can act as allosteric modulators of the Type 1 cholecystokinin receptor, Bioorganic & Medicinal Chemistry Letters, vol 18, issue 5, Pergamon, United Kingdom, pp. 4401-4404.

Qi, T., Christopoulos, G., Bailey, R.J., Christopoulos, A., Sexton, P., Hay, D.L., 2008, Identification of N-terminal receptor activity-modifying protein residues important for calcitonin gene-related peptide, adrenomedullin, and amylin receptor function, Molecular Pharmacology, vol 74, issue 4, American Society for Pharmacology and Experimental Therapeutics, United States, pp. 1059-1071.

Nawaratne, O.V., Leach, K., Suratman, S., Loiacono, R., Felder, C.C., Armbruster, B.N., Roth, B.L., Sexton, P., Christopoulos, A., 2008, New insights into the function of M4 muscarinic acetylcholine receptors gained using a novel allosteric modulator and a DREADD (designer receptor exclusively activated by a designer drug), Molecular Pharmacology, vol 74, issue 4, American Society for Pharmacology and Experimental Therapeutics, United States, pp. 1119-1131.

Werry, T.D., Stewart, G.D., Crouch, M.F., Watts, A., Sexton, P., Christopoulos, A., 2008, Pharmacology of 5HT2C receptor-mediated ERK1/2 phosphorylation: Agonist-specific activation pathways and the impact of RNA editing, Biochemical Pharmacology, vol 76, issue 10, Elsevier, United States, pp. 1276-1287.

Sexton, P., Christopoulos, G., Christopoulos, A., Nylen, E.S., Snider Jr., R.H., Becker, K.L., 2008, Procalcitonin has bioactivity at calcitonin receptor family complexes: Potential mediator implications in sepsis, Critical Care Medicine, vol 36, issue 5, Lippincott Williams & Wilkins, United Stastes, pp. 1637-1640.

Werry, T.D., Loiacono, R., Sexton, P., Christopoulos, A., 2008, RNA editing of the serotonin 5HT2C receptor and its effects on cell signalling, pharmacology and brain function, Pharmacology & Therapeutics, vol 119, issue 1, Elsevier, USA, pp. 7-23.

Morfis, M., Tilakaratne, N., Furness, S.G.B., Christopoulos, G., Werry, T.D., Christopoulos, A., Sexton, P., 2008, Receptor activity-modifying proteins differentially modulate the G protein-coupling efficiency of amylin receptors, Endocrinology, vol 149, issue 11, Endocrine Society, United States, pp. 5423-5431.

Moloney, G.P., Angus, J.A., Robertson, A.D., Stoermer, M.J., Robinson, M.S., Wright, C.E., McRae, K., Christopoulos, A., 2008, Synthesis and cannabinoid activity of 1-substituted-indole-3-oxadiazole derivatives: novel agonists for the CB1 receptor, European Journal of Medicinal Chemistry, vol 43, issue 1, Elsevier, France, pp. 513-539.

Udawela, M., Christopoulos, G., Morfis, M., Tilakaratne, N., Christopoulos, A., Sexton, P., 2008, The effects of C-terminal truncation of receptor activity modifying proteins on the induction of amylin receptor phenotype from human CTb receptors, Regulatory Peptides, vol 145, Elsevier, Amsterdam The Netherlands, pp. 65-71.

Avlani, V.A., McLoughlin, D.J., Sexton, P., Christopoulos, A., 2008, The impact of orthosteric radioligand depletion on the quantification of allosteric modulator interactions, Journal of Pharmacology and Experimental Therapeutics, vol 325, issue 3, American Society for Pharmacology and Experimental Therapeutics, United States, pp. 927-934.

Leach, K., Sexton, P., Christopoulos, A., 2007, Allosteric GPCR modulators: taking advantage of permissive receptor pharmacology, Trends in Pharmacological Sciences, vol 28, issue 8, Elsevier Science London, London England UK, pp. 382-389.

May, L.T., Leach, K., Sexton, P.M., Christopoulos, A., 2007, Allosteric modulation of G protein-coupled receptors, The Annual Review of Pharmacology and Toxicology, vol 47, Annual Reviews, Palo Alto USA, pp. 1-51.

Gregory, K.J., Sexton, P., Christopoulos, A., 2007, Allosteric modulation of muscarinic acetylcholine receptors, Current Neuropharmacology, vol 5, issue 3, Bentham Science Ltd, Sharjah, UAE, pp. 157-167.

Avlani, V.A., Gregory, K.J., Morton, C.J., Parker, M.W., Sexton, P., Christopoulos, A., 2007, Critical role for the second extracellular loop in the binding of both orthosteric and allosteric G protein-coupled receptor ligands, Journal of Biological Chemistry, vol 282, issue 35, American Society of Biochemistry & Molecular Biology Inc, Bethesda MD USA, pp. 25677-25686.

Bisson, W.H., Cheltsov, A.V., Bruey-Sedano, N., Lin, B., Chen, J., Goldberger, N., May, L.T., Christopoulos, A., Dalton, J.T., Sexton, P., Zhang, X., Abagyan, R., 2007, Discovery of antiandrogen activity of nonsteroidal scaffolds of marketed drugs, Proceedings of the National Academy of Sciences of the United States of America, vol 104, issue 29, National Academy of Sciences, Washington DC USA, pp. 11927-11932.

Urban, J.D., Clarke, W.P., von Zastrow, M., Nichols, D.E., Kobilka, B., Weinstein, H., Javitch, J.A., Roth, B.L., Christopoulos, A., Sexton, P.M., Miller, K.J., Spedding, M., Mailman, R.B., 2007, Functional selectivity and classical concepts of quantitative pharmacology, The Journal of Pharmacology and Experimental Therapeutics, vol 320, issue 1, American Society for Pharmacology and Experimental Therapeutics, Bethesda Maryland USA, pp. 1-13.

Espallergues, J., Lapalud, P., Christopoulos, A., Avlani, V.A., Sexton, P., Vamvakides, A., Maurice, T., 2007, Involvement of the sigma1 (sigma1) receptor in the anti-amnesic, but not antidepressant-like, effects of the aminotetrahydrofuran derivative ANAVEX1-41, British Journal of Pharmacology, vol 152, issue 2, Nature Publishing Group, London England UK, pp. 267-279.

May, L.T., Avlani, V.A., Langmead, C.J., Herdon, H.J., Wood, M.D., Sexton, P., Christopoulos, A., 2007, Structure-function studies of allosteric agonism at M2 muscarinic acetylcholine receptors, Molecular Pharmacology, vol 72, issue 2, American Society for Pharmacology & Experimental Therapeutics, Bethesda MD USA, pp. 463-476.

Udawela, M., Christopoulos, G., Morfis, M., Christopoulos, A., Ye, S., Tilakaratne, N., Sexton, P.M., 2006, A critical role for the short intracellular C terminus in receptor activity-modifying protein function, Molecular Pharmacology, vol 70, issue 5, American Society for Pharmacology and Experimental Therapeutics, Bethesda Maryland USA, pp. 1750-1760.

Langmead, C.J., Christopoulos, A., 2006, Allosteric agonists of 7TM receptors: expanding the pharmacological toolbox, TRENDS in Pharmacological Sciences, vol 27, issue 9, Elsevier Science, London UK, pp. 475-481.

Sexton, P., Morfis, M., Tilakaratne, N., Hay, D.L., Udawela, M., Christopoulos, G., Christopoulos, A., 2006, Complexing receptor pharmacology: modulation of family B G protein-coupled receptor function by RAMPs, Annals of the New York Academy of Sciences, vol 1070, New York Acad. Sciences, New York USA, pp. 90-104.

Hay, D.L., Christopoulos, G., Christopoulos, A., Sexton, P.M., 2006, Determinants of 1-Piperidinecarboxamide, N-[2-[[5-Amino-l-[[4-(4-pyridinyl)-l-piperazinyl]carbonyl]pentyl]amino]-1-[(3,5-dibromo-4-hydroxyphenyl)methyl]-2-oxoethyl]-4-(1,4-dihydro-2-oxo-3(2H)-quinazolinyl) (BIBN4096BS) Affinity for Calcitonin Gene-, Molecular Pharmacology, vol 70, issue 6, American Society for Pharmacology and Experimental Therapeutics, Bethesda Maryland USA, pp. 1984-1991.

Udawela, M., Christopoulos, G., Tilakaratne, N., Christopoulos, A., Albiston, A.L., Sexton, P.M., 2006, Distinct receptor activity-modifying protein domains differentially modulate interaction with calcitonin receptors, Molecular Pharmacology, vol 69, issue 6, The American Society for Pharmacology and Experimental Therapeutics, Bethesda USA, pp. 1984-1989.

Osmond, R.W., Dyer, A.R., Sexton, P.M., Christopoulos, A., Crouch, M.F., 2006, Effective GPCR screening using ERK 1/2: applying SureFire to detect ERK 1/2 phosphorylation, Genetic Engineering News, vol 26, issue 1, Mary Ann Liebert Inc, USA, pp. 27-28.

Sexton, P.M., Christopoulos, A., 2006, G protein-coupled receptor drug targets, Current Pharmaceutical Design, vol 12, issue 14, Bentham Science Publishers Ltd, Sharjah United Arab Emirates, pp. 1681-1682.

Lanzafame, A.A., Sexton, P.M., Christopoulos, A., 2006, Interaction studies of multiple binding sites on M4 muscarinic acetylcholine receptors, Molecular Pharmacology, vol 70, issue 2, The American Society for Pharmacology and Experimental Therapeutics, Bethesda USA, pp. 736-746.

Werry, T.D., Christopoulos, A., Sexton, P.M., 2006, Mechanisms of ERK1/2 regulation by seven-transmembrane-domain receptors, Current Pharmaceutical Design, vol 12, issue 14, Bentham Science Publishers Ltd, Sharjah United Arab Emirates, pp. 1683-1702.

Mathiesen, J.M., Christopoulos, A., Ulven, T., Royer, J.F., Campillo, M., Heinemann, A., Pardo, L., Kostenis, E., 2006, On the mechanism of interaction of potent surmountable and insurmountable antagonists with the prostaglandin D2 receptor CRTH2, Molecular Pharmacology, vol 69, issue 4, American Society for Pharmacology and Experimental Therapeutics, Bethesda Maryland USA, pp. 1441-1453.

Langmead, C.J., Fry, V.A., Forbes, I.T., Branch, C.L., Christopoulos, A., Wood, M.D., Herdon, H.J., 2006, Probing the molecular mechanism of interaction between 4-n-butyl-1-[4-(2- methylphenyl)-4-oxo-1-butyl]-piperidine (AC-42) and the muscarinic M1 receptor: Direct pharmacological evidence that AC-42 is an allosteric agonist, Molecular Pharmacology, vol 69, issue 1, The American Society for Pharmacology and Experimental Therapeutics, Bethesda USA, pp. 236-246.

Price, M.R., Baillie, G.L., Thomas, A., Stevenson, L.A., Easson, M., Goodwin, R., McLean, A., McIntosh, L., Goodwin, G., Walker, G., Westwood, P., Marrs, J., Thomson, F., Cowley, P., Christopoulos, A., Pertwee, R.G., Ross, R.A., 2005, Allosteric modulation of the cannabinoid CB1 receptor, Molecular Pharmacology, vol 68, issue 5, American Society for Pharmacology and Experimental Therapeutics, USA, pp. 1484-1495.

Werry, T.D., Gregory, K.J., Sexton, P.M., Christopoulos, A., 2005, Characterization of serotonin 5-HT2C receptor signaling to extracellular signal-regulated kinases 1 and 2, Journal of Neurochemistry, vol 93, Blackwell Publishing, Oxford UK, pp. 1603-1615.

May, L.T., Sexton, P.M., Christopoulos, A., 2005, Effects of urea pretreatment on the binding properties of adenosine A 1 receptors, British Journal of Pharmacology, vol 146, issue 8, Nature Publishing Group, UK, pp. 1119-1129.

Hutchinson, D.S., Sato, M., Evans, B.A., Christopoulos, A., Summers, R.J., 2005, Evidence for pleiotropic signaling at the mouse beta3-adrenoceptor revealed by SR59230A [3-(2-ethylphenoxy)-1-[(1,S)-1,2,3,4-tetrahydronapth-1-ylamino]-2S-2-propanol oxalate], The Journal of Pharmacology and Experimental Therapeutics, vol 312, issue 3, American Society for Pharmacology and Experimental Therapeutics, Bethesda USA, pp. 1064-1074.

Kostenis, E., Milligan, G., Christopoulos, A., Sanchez-Ferrer, C.F., Heringer-Walther, S., Sexton, P.M., Gembardt, F., Kellett, E., Martini, L., Vanderheyden, P., Schultheiss, H., Walther, T., 2005, G-protein-coupled receptor Mas is a physiological antagonist of the angiotensin II type 1 receptor, Circulation, vol 111, Lippincott Williams & Wilkins, Philadelphia USA, pp. 1806-1813.

Werry, T.D., Sexton, P.M., Christopoulos, A., 2005, 'Ins and outs' of seven-transmembrane receptor signalling to ERK, Trends in Endocrinology and Metabolism, vol 16, issue 1, Elsevier Science London, UK, pp. 26-33.

Hay, D.L., Christopoulos, G., Christopoulos, A., Poyner, D.R., Sexton, P.M., 2005, Pharmacological discrimination of calcitonin receptor: receptor activity-modifying protein complexes, Molecular Pharmacology, vol 67, issue 5, American Society for Pharmacology and Experimental Therapeutics, Bethesda MD USA, pp. 1655-1665.

May, L.T., Lin, Y., Sexton, P.M., Christopoulos, A., 2005, Regulation of M2 muscarinic acetylcholine receptor expression and signaling by prolonged exposure to allosteric modulators, The Journal of Pharmacology and Experimental Therapeutics, vol 312, issue 1, American Society for Pharmacology and Experimental Therapeutics, USA, pp. 382-390.

May, L.T., Avlani, V.A., Sexton, P., Christopoulos, A., 2004, Allosteric modulation of G protein-coupled receptors, Current Pharmaceutical Design [P], vol 10, issue 17, Bentham Science Publishers Ltd, The Netherlands, pp. 2003-2013.

Hay, D.L., Christopoulos, G., Christopoulos, A., Sexton, P., 2004, Amylin receptors: Molecular composition and pharmacology, Biochemical Society Transactions [P], vol 32, issue Pt 5, Portland Press Ltd, UK, pp. 865-867.

Avlani, V.A., May, L.T., Sexton, P., Christopoulos, A., 2004, Application of a kinetic model to the apparently complex behavior of negative and positive allosteric modulators of muscarinic acetylcholine receptors, The Journal of Pharmacology and Experimental Therapeutics, vol 308, issue 3, American Society for Pharmacology and Experimental Therapeutics, USA, pp. 1062-1072.

Christopoulos, A., May, L.T., Avlani, V.A., Sexton, P.M., 2004, G-protein-coupled receptor allosterism: the promise and the problem(s), Biochemical Society Transactions [P], vol 32, issue Pt 5, Portland Press Ltd, UK, pp. 873-877.

Devlin, M.G., Smith, N.J., Ryan, O.M., Guida, E., Sexton, P.M., Christopoulos, A., 2004, Regulation of serotonin 5-HT{2C} receptors by chronic ligand exposure, European Journal of Pharmacology, vol 498, issue 1-3, Elsevier Science BV, The Netherlands, pp. 59-69.

Christopoulos, A., Christopoulos, G., Morfis, M., Udawela, M., Laburthe, M., Couvineau, A., Kuwasako, K., Tilakaratne, N., Sexton, P.M., 2003, Novel receptor partners and function of receptor activity-modifying proteins, Journal of Biological Chemistry, vol 278, issue 5, American Society for Biochemistry and Molecular Biology, Inc., Bethesda USA, pp. 3293-3297.

Morfis, M., Christopoulos, A., Sexton, P., 2003, RAMPs: 5 years on, where to now?, Trends in Pharmacological Sciences, vol 24, issue 11, Elsevier Science London, UK, pp. 596-601.

Christopoulos, A., Kenakin, T., 2002, G protein-coupled receptor allosterism and complexing, Pharmacological Reviews, vol 54, issue 2, American Society for Pharmacology and Experimental Therapeutics, Bethesda MD USA, pp. 323-374.

Lyon, G.J., Wright, J.S., Christopoulos, A., Novick, R.P., Muir, T.W., 2002, Reversible and specific extracellular antagonism of receptor-histidine kinase signaling, Journal of Biological Chemistry, vol 277, issue 8, American Society for Biochemistry and Molecular Biology, Inc., Bethesda USA, pp. 6247-6253.

Lanzafame, A., Christopoulos, A., Mitchelson, F., 2001, The allosteric interaction of otenzepad (AF-DX 116) at muscarinic M2 receptors in guinea-pig atria, European Journal of Pharmacology, vol 416, Elsevier Science BV, Netherlands, pp. 235-244.

Christopoulos, A., Sorman, J.L., Mitchelson, F.J., El-Fakahany, E.E., 1999, Characterization of the subtype selectivity of the all osteric modulator heptan-1,7-bis-(dimethyl-3'- phthalimidopropl)ammonium bromide(C7/3-phth)at cloned muscarine acetycholine receptors, Biochemical Pharmacology, vol 57 issue 2, Elsevier Science, Netherlands, pp. 171-179.

Christopoulos, A., Lanzafame, A., Mitchelson, F.J., 1998, Allosteric interactions at muscarinic cholinoceptors, Clinical and Experimental Pharmacology and Physiology, vol 25, Blackwell Science, Australia, pp. 185-194.

Christopoulos, A., Mitchelson, F.J., 1998, Use of a spreadsheet to quantitate the equilibrium binding of an allosteric modulator, European Journal of Pharmacology, vol 355, Elsevier Science, Netherlands, pp. 103-111.

Christopoulos, A., Mitchelson, F., 1997, Application of an allosteric ternary complex model to the technique of pharmacological resultant analysis, Journal of Pharmacy and Pharmacology, vol 49, Pharmaceutical Press, UK, pp. 781-786.

Gilani, A.H., Shaheen, F., Christopoulos, A., Mitchelson, F., 1997, Interaction of ebeinone, an alkaloid from Fritillaria imperialis, at two muscrinic acetylcholine receptor subtypes, Life Sciences, vol 60, Elsevier Sciences Inc, USA, pp. 535-544.

Christopoulos, A., Lanzafame, A., Ziegler, A., Mitchelson, F., 1997, Kinetic studies of co-operativity ar atrial muscarinic M2 receptors with an "Infinite Dilution" procedure, Biochemical Pharmacology, vol 53, Elsevier Science Inc, USA, pp. 795-800.

Christopoulos, A., Mitchelson, F., 1997, Pharmacological analysis of the mode of interaction of McN-A-343 at atrial muscarinic M2 receptors, European Journal of Pharmacology, vol 339, Elsevier, Netherlands, pp. 153-156.

Lanzafame, A., Christopoulos, A., Mitchelson, F., 1997, Three all osteric modulators act at a common site, distinct from that of competitive antahonists, at muscarinic acetylcholine M2 receptors, Journal of Pharmacology and Experimental Therapeutics, vol 282, Am Soc for Pharmacol & Experimental Therapeutics, USA, pp. 278-285.

Conference Proceedings

Christopoulos, A., 2006, GPCR allosterism: A novel approach to drug selectivity, Acta Pharmacologica Sinica, 2 July 2006 to 7 July 2006, Blackwell Publishing, Oxford England, p. 9.

Christopoulos, A., 2006, Non-classical modes of signaling by 5HT(2C) receptors, Journal of Pharmacological Sciences, 26 June 2006 to 30 June 2006, Japanese Pharmacological Society, Kyoto Japan, p. 55.

El-Fakahany, E.E., Christopoulos, A., Sorman, J.L., Mitchelson, F.J., 1998, Characterization of the subtype selectivity of the allosteric modulator, C7/ 3 - PHTH, at cloned muscarinic acetylcholine receptors, Subtypes of Muscarinic Receptors, 25 August 1998 to 29 August 1998, Boston University Press, Massachusetts USA, p. 14.

Mitchelson, F.J., Lanzafame, A., Christopoulos, A., 1998, The interaction of otenzepad (AF- DX 116) with allosteric modulators and competitive antagonists at a muscarinic M2 receptor, Subtypes of Muscarinic Receptors, 25 August 1998 to 29 August 1998, Boston University Press, Massachusetts USA, p. 9.

Christopoulos, A., Lanzafame, A., Mitchelson, F., 1997, A common site of action for two allosteric antagonists, Life Sciences, 12 November 1996 to 15 November 1996, Elsevier Science, USA, p. 1173.

Lanzafame, A., Christopoulos, A., Mitchelson, F., 1997, The allosteric interaction of otenzepad at muscarinic acetylcholine M2 receptors in cardiac tissue, Proceedings of ASCEPT: Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists, ASCEPT, Australia, p. 47.

Other

Scammells, P.J., Aurelio, L., Christopoulos, A., Sexton, P., Valant, C., Flynn, B.L., Linden, J., 2009, A1 adenosine receptor allosteric enhancers, USA, AU.

Teaching Commitment

  • Lectures to second year BPharm students in the Faculty of Pharmacy and Pharmaceutical Sciences
  • Lectures to third year BPharmSci students in the Faculty of Pharmacy and Pharmaceutical Sciences
  • Supervision of Honours students in Drug Discovery Biology
  • Supervision of PhD students in Drug Discovery Biology

Activities

Affiliations with institutes

Theme Leader
Drug Discovery Biology
Monash Institute of Pharmaceutical Sciences

Grants

Title:
Understanding Allosteric Modulation and Functional Selectivity at G Protein-Coupled Receptors.
Investigators:
Scammells, P, Christopoulos, A
Funding:
(2011 - 2013). Australian Research Council (ARC) [arc, AUS, ACT].
(2011 - 2013). Monash University [monash, AUS, VIC].
Title:
High throughput analysis and screening facility.
Investigators:
Sexton, P, Christopoulos, A, Whisstock, J, Rossjohn, J, Scammells, P, Drummond, G, Beddoe, T, Mackay, C, Charman, W, Hertzog, P
Funding:
(2009). National Health & Medical Research Council (NHMRC) [nhmrc, AUS, ACT].
Title:
Understanding the pharmacoregulation of the extracellular calcium sensing receptor.
Investigators:
Christopoulos, A, Conigrave, A
Funding:
(2009 - 2011). National Health & Medical Research Council (NHMRC) [nhmrc, AUS, ACT].
Title:
Understanding G Protein-coupled receptors (GPCRs): Accelerating discovery from concept to clinic.
Investigators:
Sexton, P, Christopoulos, A, Summers, R
Funding:
(2009 - 2013). National Health & Medical Research Council (NHMRC) [nhmrc, AUS, ACT].
Title:
Allosteric Modulators as Novel Probes of G-Protein Coupled Receptor Function.
Investigators:
Scammells, P, Christopoulos, A, Flynn, B
Funding:
(2008 - 2010). Australian Research Council (ARC) [arc, AUS, ACT].
Title:
Novel modes of signalling of serotonin 5_HT2c receptors.
Investigators:
Christopoulos, A, Crouch, M, Stewart, G
Funding:
(2005 - 2008). Australian Research Council (ARC) [arc, AUS, ACT].
(2005 - 2008). TGR BioSciences Pty Ltd [tgrbio, AUS, SA].
Title:
HTS Cell Based EFC Assays for GPCR Drug Discovery.
Investigators:
Christopoulos, A
Funding:
(2006). National Institutes of Health (NIH) [nih, USA, MD].
Title:
Allosteric regulation of G protein-coupled receptors.
Investigators:
Christopoulos, A, Sexton, P, Tobin, A, Abagyan, R
Funding:
(2006 - 2008). National Health & Medical Research Council (NHMRC) [nhmrc, AUS, ACT].
Title:
Novel modes of regulating serotonin 5HT2c receptors.
Investigators:
Christopoulos, A, Sexton, P
Funding:
(2006 - 2008). National Health & Medical Research Council (NHMRC) [nhmrc, AUS, ACT].
Title:
NHMRC Research Fellowship.
Investigators:
Christopoulos, A
Funding:
(2006 - 2020). National Health & Medical Research Council (NHMRC) [nhmrc, AUS, ACT].
Title:
Molecular mechanisms underlying G protein coupled receptor signaling.
Investigators:
Sexton, P, Christopoulos, A, Summers, R, Eidne, K
Funding:
(2006). National Health & Medical Research Council (NHMRC) [nhmrc, AUS, ACT].
Title:
Molecular pharmacology of receptor activity modifying protein (RAMP) action.
Investigators:
Sexton, P, Christopoulos, A, Tilakaratne, N, Summers, R
Funding:
(2006). National Health & Medical Research Council (NHMRC) [nhmrc, AUS, ACT].

Postgraduate Research Supervisions

Current Supervision

Program of Study:
(DOCTORATE BY RESEARCH).
Thesis Title:
Adenosine Receptor-Mediated Attenuation of Organ Transplant Rejection.
Supervisors:
May, L (Main), Christopoulos, A (Associate), White, P (Associate).
Program of Study:
(DOCTORATE BY RESEARCH).
Thesis Title:
Allosteric Targeting of the dopamine D2 receptor.
Supervisors:
Lane, J (Main), Christopoulos, A (Associate).
Program of Study:
(DOCTORATE BY RESEARCH).
Thesis Title:
Allosteric modulation of M4 muscarinic acetylcholine receptors..
Supervisors:
Christopoulos, A (Main), Canals, M (Associate).
Program of Study:
(DOCTORATE BY RESEARCH).
Thesis Title:
BIASED ALLOSTERIC MODULATORS OF METABOTROPIC GLUTAMATE RECEPTOR 5.
Supervisors:
Gregory, K (Main), Christopoulos, A (Associate).
Program of Study:
(DOCTORATE BY RESEARCH).
Thesis Title:
Effect of allosteric modulation of the muscarinic M4 and M5 receptors in drug-seeking behaviours.
Supervisors:
Christopoulos, A (Main), Langmead, C (Associate).
Program of Study:
(DOCTORATE BY RESEARCH).
Thesis Title:
M4 Muscarinic Acetylcholine Receptor Modulation of Dopamine Receptor Functions.
Supervisors:
Malone, D (Main), Canals, M (Associate), Christopoulos, A (Associate).
Program of Study:
(DOCTORATE BY RESEARCH).
Thesis Title:
Structure-function analysis of orthosteric, allosteric and bitopic ligand binding at Adenosine A1 receptor.
Supervisors:
Christopoulos, A (Main), May, L (Associate).
Program of Study:
(DOCTORATE BY RESEARCH).
Thesis Title:
Understanding novel drug binding pockets of G-protein coupled receptors.
Supervisors:
Christopoulos, A (Main), Valant, C (Associate).

Completed Supervision

Student:
Abdul Ridha, A.
Program of Study:
Pharmacological and Stucture-Function Studies of M1 Muscarinic Acetylcholine Receptor Allosteric Modulation. (PHD) 2014.
Supervisors:
Christopoulos, A (Joint-Co), Canals, M (Joint).
Student:
Cook, A.
Program of Study:
Stimulus bias at the calcium sensing receptor. (PHD) 2013.
Supervisors:
Christopoulos, A (Main).
Student:
Davie, B.
Program of Study:
Synthesis and pharmacological investigation of allosteric and bitopic ligands for the M1 muscarinic acetylcholine receptor. (PHD) 2014.
Supervisors:
Christopoulos, A (Joint-Co), Scammells, P (Joint), Capuano, B (Associate).
Student:
Gregory, K.
Program of Study:
Allosteric modulation of M2 muscarinic acetylcholine receptors. (PHD) 2009.
Supervisors:
Christopoulos, A (Main), Sexton, P (Associate).
Student:
Keov, P.
Program of Study:
Structural and mechanistic studies of novel selective agonists of the M1 muscarinic acetylcholine receptor. (PHD) 2014.
Supervisors:
Christopoulos, A (Main), Lane, J (Associate), Valant, C (Associate).
Student:
Klein Herenbrink, C.
Program of Study:
Understanding biased agonism at the dopamine D2 receptor. (PHD) 2016.
Supervisors:
Lane, J (Main), Christopoulos, A (Associate).
Student:
Koole, C.
Program of Study:
Pharmacological and structure-function analysis of the human glucagon-like peptide-1 receptor. (PHD) 2011.
Supervisors:
Sexton, P (Main), Christopoulos, A (Associate).
Student:
Nawaratne, O.
Program of Study:
Structure-function studies of M4 muscarinic acetylcholine receptor allosteric modulation. (PHD) 2011.
Supervisors:
Christopoulos, A (Main), Sexton, P (Associate).
Student:
Stewart, G.
Program of Study:
Pharmacological profiling of G protein-coupled receptors using Saccharomyces cerevisiae. (PHD) 2009.
Supervisors:
Christopoulos, A (Joint-Co), Sexton, P (Joint).
Student:
Szabo, M.
Program of Study:
Medicinal chemistry techniques to gain selectivity at G protein-coupled receptors targeting the CNS. (PHD) 2014.
Supervisors:
Capuano, B (Joint-Co), Christopoulos, A (Joint).
Student:
Thompson, G.
Program of Study:
Biased agonism at the mu-opioid receptor. (PHD) 2016.
Supervisors:
Canals, M (Main), Christopoulos, A (Associate).