Research Papers

Merlin J, Park J, Vandekolk TH, Fabb SA, Allinne J, Summers RJ, Langmead CJ, Riddy DM (2022). Multipathway In Vitro Pharmacological Characterization of Specialized Proresolving G Protein-Coupled Receptors. Mol Pharmacol 101(4):246-256. doi: 10.1124/molpharm.121.000422.

Spark DL,  Vermeulen MH,  Rueda P,  De La Fuente Gonzalez R, Sepehrizadeh T,  De Veer M,  Mannoury la Cour C,  Fornito A, Langiu M, Stewart GD, Nithianantharajah J, Langmead CJ (2022). Gpr88 deletion impacts motivational control independently of striatal dopamine function. bioRxiv 2022.05.19.492565 doi: 10.1101/2022.05.19.492565

Zhao P, Truong TT, Merlin J, Sexton PM, Wootten D (2022). Implications of ligand-receptor binding kinetics on GLP-1R signalling. Biochem Pharmacol 199:114985. doi: 10.1016/j.bcp.2022.114985.

Walker LC, Campbell EJ, Huckstep KL, Chen NA, Langmead CJ, Lawrence AJ (2022). M₁ muscarinic receptor activation decreases alcohol consumption via a reduction in consummatory behavior. Pharmacol Res Perspect 10(1): e00907. doi: 10.1002/prp2.907.

Riddy DM, Kammoun HL, Murphy AJ, Bosnyak-Gladovic S, De la Fuente Gonzalez R, Merlin J, Ziemann M, Fabb S, Pierce TL, Diepenhorst N, Rueda P, El-Osta A, Gautier JF, Venteclef N, Charman WN, Christopoulos A, Sexton PM, Summers RJ, Febbraio MA, Delerive P, Langmead CJ (2021). Deletion of GPR21 improves glucose homeostasis and inhibits the CCL2-CCR2 axis by divergent mechanisms. BMJ Open Diabetes Res Care 9(2):e002285. doi: 10.1136/bmjdrc-2021-002285.

Brown AJH, Bradley SJ, Marshall FH, Brown GA, Bennett KA, Brown J, Cansfield JE, Cross DM, de Graaf C, Hudson BD, Dwomoh L, Dias JM, Errey JC, Hurrell E, Liptrot J, Mattedi G, Molloy C, Nathan PJ, Okrasa K, Osborne G, Patel JC, Pickworth M, Robertson N, Shahabi S, Bundgaard C, Phillips K, Broad LM, Goonawardena AV, Morairty SR, Browning M, Perini F, Dawson GR, Deakin JFW, Smith RT, Sexton PM, Warneck J, Vinson M, Tasker T, Tehan BG, Teobald B, Christopoulos A, Langmead CJ, Jazayeri A, Cooke RM, Rucktooa P, Congreve MS, Weir M, Tobin AB (2021). From structure to clinic: Design of a muscarinic M1 receptor agonist with potential to treatment of Alzheimer's disease. Cell 184(24):5886-5901.e22. doi: 10.1016/j.cell.2021.11.001.

Burger WAC, Gentry PR, Berizzi AE, Vuckovic Z, van der Westhuizen ET, Thompson G, Yeasmin M, Lindsley CW, Sexton PM, Langmead CJ, Tobin AB, Christopoulos A, Valant C, Thal DM (2021). Identification of a novel allosteric site at the M₅ muscarinic acetylcholine receptor.  ACS Chem Neurosci 12(16):3112-3123. doi: 10.1021/acschemneuro.1c00383.

Walker LC, Huckstep KL, Chen NA, Hand LJ, Lindsley CW, Langmead CJ, Lawrence AJ (2021). Muscarinic M₄ and M₅ receptors in the ventral subiculum differentially modulate alcohol seeking versus consumption in male alcohol-preferring rats.  Br J Pharmacol 178(18):3730-3746. doi: 10.1111/bph.15513.

Nair PC, Miners JO, McKinnon RA, Langmead CJ, Gregory KJ, Copolov D, Chan SKW, Bastiampillai T (2021). Binding of SEP-363856 within TAAR1 and the 5HT_1A receptor: implications for the design of novel antipsychotic drugs.  Mol Psychiatry 27(1):88-94. doi: 10.1038/s41380-021-01250-7.

Johnson RM, Zhang X, Piper SJ, Nettleton TJ, Vandekolk TH, Langmead CJ, Danev R, Sexton PM, Wootten D (2021). Cryo-EM structure of the dual incretin receptor agonist, peptide-19, in complex with the glucagon-like peptide-1 receptor. Biochem Biophys Res Commun 578:84-90. doi: 10.1016/j.bbrc.2021.09.016.

Giuffrida L, Sek K, Henderson MA, Lai J, Chen AXY, Meyran D, Todd KL, Petley EV, Mardiana S, Mølck C, Stewart GD, Solomon BJ, Parish IA, Neeson PJ, Harrison SJ, Kats LM, House IG, Darcy PK, Beavis PA (2021). CRISPR/Cas9 mediated deletion of the adenosine A2A receptor enhances CAR T cell efficacy.  Nat Comm 12,  Article number:3236 doi.org/10.1038/s41467-021-23331-5.

Rueda P, Merlin J, Chimenti S, Feletou M, Paysant J, White PJ, Christopoulos A, Sexton PM, Summers RJ, Charman WN, May LT, Langmead CL (2021). Pharmacological insights into safety and efficacy determinants for the development of adenosine receptor biased agonists in the treatment of heart failure. Front Pharmacol 12: 628060  doi.org/10.3389/fphar.2021.628060.

Zhang X, Belousoff MJ, Zhao P, Kooistra AJ, Truong TT, Ang SY, Underwood CR, Egebjerg T, Šenel P, Stewart GD, Liang Y-L, Glukhova A, Venugopal H, Christopoulos A, Furness SGB, Miller LJ, Reedtz-Runge S, Langmead CJ, Gloriam DE, Danev R, Sexton PM, Wootten D (2020). Differential GLP-1R binding and activation by peptide and non-peptide agonists. Mol Cell 80(3):485-500. e7. doi: 10.1016/j.molcel.2020.09.020.

Spark DL, Mao M, Ma S, Sarwar M, Nowell CJ, Shackleford DM, Sexton PM, Nithianantharajah J, Stewart GD, Langmead CJ (2020). In the loop: Extrastriatal regulation of spiny projection neurons by GPR52.  ACS Chem Neurosci 11(14): 2066–2076 doi.org/10.1021/acschemneuro.0c00197.

Hatzipantelis CJ, Lu Y, Spark DL, Langmead CJ, Stewart GD (2020). β-Arrestin-2-dependent mechanism of GPR52 signaling in frontal cortical neurons. ACS Chem Neurosci. 11(14): 2077–2084 doi.org/10.1021/acschemneuro.0c00199.

Hellmann J, Drabek M, Yin J, Gunera J, Pröll T, Frank Kraus F, Langmead CJ, Hübner H, Weikert D, Kolb P, Rosenbaum DM, Gmeiner P (2020). Structure-based development of a subtype-selective orexin 1 receptor antagonist. PNAS 117(30): 18059-18067  doi.org/10.1073/pnas.2002704117.

Walker LC,  Berizzi AE, Chen NA , Rueda P, Perreau VM , Huckstep K, Srisontiyakul J, Govitrapong P, Xiaojian J, Lindsley C W, Jones CK, Riddy DM, Christopoulos A, Langmead CJ, Lawrence AJ (2020). Acetylcholine muscarinic M₄ receptors as a therapeutic target for alcohol use disorder: Converging evidence from humans and rodents.  Biol Psychiatry 88(12):898-909. doi: 10.1016/j.biopsych.2020.02.019.

Josephs TM, Keller AN, Khajehali E, DeBono A, Langmead CJ, Conigrave AD, Capuano B, Kufareva I, Gregory KJ, Leach K (2020). Negative allosteric modulators of the human calcium-sensing receptor bind to overlapping and distinct sites within 7-transmembrane domain.  Br J Pharmacol 177(8):1917-1930. doi: 10.1111/bph.14961.

Ramírez-García PD, Retamal JS, Shenoy P, Imlach W, Sykes M, Truong N, Constandil L, Pelissier T, Nowell CJ, Khor SY, Layani LM, Lumb C, Poole DP, Lieu T, Stewart GD, Mai QN, Jensen DD, Latorre R, Scheff NN, Schmidt BL, Quinn JF, Whittaker MR, Veldhuis NA, Davis TP, Bunnett NW (2019). A pH-responsive nanoparticle targets the neurokinin 1 receptor in endosomes to prebvent chronic pain.  Nat Nanotechnol 14(12):1150-1159. doi: 10.1038/s41565-019-0568-x.

Vuckovic Z, Gentry PR, Berizzi AE, Hirata K, Varghese S, Thompson G, van der Westhuizen ET, Burger WAC, Rahmani R, Valant C, Langmead CJ, Lindsley CW, Baell JB, Tobin AB, Sexton PM, Christopoulos A, Thal DM. (2019) Crystal structure of the M₅ muscarinic acetylcholine receptor.  Proc Natl Acad Sci USA 116(51):26001-26007. doi: 10.1073/pnas.1914446116.

Riddy DM, Cook AE, Shackleford DM, Pierce TL, Mocaer E, Mannoury la Cour C, Sors A, Charman WN, Summers RJ, Sexton PM, Christopoulos A, Langmead CJ (2019). Drug-receptor kinetics and sigma-1 receptor affinity differentiate clinically evaluated histamine H₃ receptor antagonists.  Neuropharmacology 144:244-255. doi: 10.1016/j.neuropharm.2018.10.028.

Riddy DM, Goy E, Delerive P, Summers RJ, Sexton PM, Langmead CJ (2018). Comparative genotypic and phenotypic analysis of human peripheral blood monocytes and surrogate monocyte-like cell lines commonly used in metabolic disease research.  PLoS One 13(5):e0197177. doi: 10.1371/journal.pone.0197177.

Stewart GD,  Comps-Agrar L, Nørskov-Lauritsen LB,  Pin J-P, Kniazeff J (2018). Allosteric interactions between GABA B1 subunits control orthosteric binding sites occupancy within GABA B oligomers.  Neuropharmacology 136(Pt A):92-101. doi: 10.1016/j.neuropharm.2017.12.042.

Bradley SJ, Molloy C, Bundgaard C, Mogg AJ, Thompson KJ, Dwomoh L, Sanger HE, Crabtree MD, Brooke SM, Sexton PM, Felder CC, Christopoulos A, Broad LM, Tobin AB, Langmead CJ (2018). Bitopic binding mode of an M₁ muscarinic acetylcholine receptor agonist associated with adverse clinical trial outcomes.  Mol Pharmacol 93(6):645-656. doi: 10.1124/mol.118.111872.

Berizzi AE, Perry CJ, Shackleford DM, Lindsley CW, Jones CK, Chen NA, Sexton PM, Christopoulos A, Langmead CJ, Lawrence AJ (2018). Muscarinic M₅ receptors modulate ethanol seeking in rats.  Neuropsychopharmacology 43(7):1510-1517. doi: 10.1038/s41386-017-0007-3.

Berizzi AE, Bender AM, Lindsley CW, Conn PJ, Sexton PM, Langmead CJ, Christopoulos A (2018). Structure-activity relationships of Pan-Gα_q/11 coupled muscarinic acetylcholine receptor positive allosteric modulators.  ACS Chem Neurosci 9(7):1818-1828. doi: 10.1021/acschemneuro.8b00136.

Bender AM, Cho HP, Nance KD, Lingenfelter KS, Luscombe VB, Gentry PR, Voigtritter K, Berizzi AE, Sexton PM, Langmead CJ, Christopoulos A, Locuson CW, Bridges TM, Chang S, O'Neill JC, Zhan X, Niswender CM, Jones CK, Conn PJ, Lindsley CW (2018). Discovery and optimization of potent and CNS penetrant M₅-preferring positive allosteric modulators derived from a novel chiral N-(indanyl)piperidine amide scaffold.  ACS Chem Neurosci 9(7):1572-1581. doi: 10.1021/acschemneuro.8b00126.

Diepenhorst NA, Leach K, Keller AN, Rueda P, Cook AE, Pierce TL, Nowell C, Pastoureau P, Sabatini M, Summers RJ, Charman WN, Sexton PM, Christopoulos A, Langmead CJ (2018). Divergent effects of strontium and calcium-sensing receptor positive allosteric modulators (calcimimetics) on human osteoclast activity.  Br J Pharmacol. 175(21):4095-4108. doi: 10.1111/bph.14344.

Sengmany K, Singh J, Stewart GD, Conn PJ, Christopoulos A, Gregory KJ (2017). Biased allosteric agonism and modulation of metabotropic glutamate receptor 5: Implications for optimizing preclinical neuroscience drug discovery.  Neuropharmacology 115:60-72. doi: 10.1016/j.neuropharm.2016.07.001.

Riddy DM, Cook AE, Diepenhorst NA, Bosnyak S, Brady R, Mannoury la Cour C, Mocaer E, Summers RJ, Charman WN, Sexton PM, Christopoulos A, Langmead CJ (2017).  Isoform-specific biased agonism of histamine H₃ receptor agonists.  Mol Pharmacol 91(2):87-99. doi: 10.1124/mol.116.106153. Erratum in: Mol  Pharmacol 91(3):263, 2017

Diepenhorst NA, Nowell CJ, Rueda P, Henriksen K, Pierce T, Cook AE, Pastoureau P, Sabatini M, Charman WN, Christopoulos A, Summers RJ, Sexton PM, Langmead CJ (2017). High throughput, quantitative analysis of human osteoclast differentiation and activity.  Anal Biochem 2017 519:51-56. doi: 10.1016/j.ab.2016.12.010.

Mølck C, Ryall J, Failla LM, Coates JL, Pascussi J-M, Heath JK, Stewart GD, Hollande F (2016). The A 2b adenosine receptor antagonist PSB-603 promotes oxidative phosphorylation and ROS production in colorectal cancer cells via adenosine receptor-independent mechanism. Cancer Letters 383(1):135-143. doi: 10.1016/j.canlet.2016.09.018.

Rueda P, Harley E, Lu Y, Stewart GD, Fabb S, Diepenhorst N, Cremers B, Rouillon MH, Wehrle I, Geant A, Lamarche G, Leach K, Charman WN, Christopoulos A, Summers RJ, Sexton PM, Langmead CJ (2016). Murine GPRC6A mediates cellular responses to L-amino acids, but not osteocalcin variants.  PLoS One 11(1):e0146846. doi: 10.1371/journal.pone.0146846.

Choy KH, Shackleford DM, Malone DT, Mistry SN, Patil RT, Scammells PJ, Langmead CJ, Pantelis C, Sexton PM, Lane JR, Christopoulos A (2016). Positive allosteric modulation of the muscarinic M1 receptor improves efficacy of antipsychotics in mouse glutamatergic deficit models of behavior.  J Pharmacol Exp Ther 359(2):354-365. doi: 10.1124/jpet.116.235788.

Berizzi AE, Gentry PR, Rueda P, Den Hoedt S, Sexton PM, Langmead CJ, Christopoulos A (2016). Molecular mechanisms of action of M5 muscarinic acetylcholine receptor allosteric modulators.  Mol Pharmacol 90(4):427-36. doi: 10.1124/mol.116.104182.

Riddy DM, Valant C, Rueda P, Charman WN, Sexton PM, Summers RJ, Christopoulos A, Langmead CJ (2015). Label-free kinetics: Exploiting functional hemi-equilibrium to derive rate constants for muscarinic receptor antagonists.  Mol Pharmacol 88(4):779-90. doi: 10.1124/mol.115.100545.

Books

Langmead CJ (ed). Advances in Pharmacology: From Structure to Clinical Development: Allosteric Modulation of G Protein-Coupled Receptors. Cambridge, MA, Elsevier. 2020 doi: 10.1016/S1054-3589(20)30037-5

Reviews & Editorials

Piper NBC, Whitfield EA, Stewart GD, Xu X, Furness SGB (2022), Targeting appetite and satiety in diabetes and obesity, via G protein-coupled receptors, Biochemical Pharmacology (202). doi.org/10.1016/j.bcp.2022.115115.

Spark DL, Fornito A, Langmead CJ, Stewart GD (2022). Beyond antipsychotics: a twenty-first century update for preclinical development of schizophrenia therapeutics, Transl Psychiatry (in press). doi: 10.1038/s41398-022-01904-2. (no longer 'in press')

Nair PC, Chalker JM, McKinnon RA, Langmead CJ, Gregory KJ, Bastiampillai T (2022). Trace Amine-Associated Receptor 1 (TAAR1): Molecular and Clinical Insights for the Treatment of Schizophrenia and Related Comorbidities. ACS Pharmacol Transl Sci 5(3):183-188. doi: 10.1021/acsptsci.2c00016.

Hatzipantelis CJ, Langiu M, Vandekolk TH, Pierce TL, Nithianantharajah J, Stewart GD, Langmead CJ (2020). Translation-Focused Approaches to GPCR Drug Discovery for Cognitive Impairments Associated with Schizophrenia. ACS Pharmacol Transl Sci 3(6): 1042–1062. doi: 10.1021/acsptsci.0c00117.

Park J, Langmead CJ, Riddy DM. (2020)  New advances in targeting the resolution of inflammation:  Implications for specialized pro-resolving mediator GPCR drug discovery.  ACS Pharmacol Transl Sci 3(1):88-106. doi: 10.1021/acsptsci.9b00075.

Gogos A, Langmead C, Sullivan JC, Lawrence, AJ. (2019) The importance of sex differences in pharmacology research. Br J Pharmacol 176 (21): 4087-4089. doi: 10.1111/bph.14819.

Sek K, Mølck C, Stewart GD, Kats L, Darcy PK, Beavis PA (2018) Targeting adenosine receptor signaling in cancer immunotherapy. Int J Mol Sci 19(12):3837. doi: 10.3390/ijms19123837.

Langmead CJ, Summers RJ. (2018) Molecular pharmacology of GPCRs.  Br J Pharmacol 175(21):4005-4008. doi: 10.1111/bph.14474.

Riddy DM, Delerive P, Summers RJ, Sexton PM, Langmead CJ. (2018) G protein-coupled receptors targeting insulin resistance, obesity and type 2 diabetes mellitus.  Pharmacol Rev 70(1):39-67. doi: 10.1124/pr.117.014373.

Diepenhorst N, Rueda P, Cook AE, Pastoureau P, Sabatini M, Langmead CJ. (2018)  G protein-coupled receptors as anabolic drug targets in osteoporosis.  Pharmacol Ther 184:1-12. doi: 10.1016/j.pharmthera.2017.10.015.

Christopoulos A, Changeux JP, Catterall WA, Fabbro D, Burris TP, Cidlowski JA, Olsen RW, Peters JA, Neubig RR, Pin JP, Sexton PM, Kenakin TP, Ehlert FJ, Spedding M, Langmead CJ. (2014)  International Union of Basic and Clinical Pharmacology.XC. multisite pharmacology:  recommendations for the nomenclature of receptor allosterism and allosteric ligands.  Pharmacol Rev 66(4):918-47. doi: 10.1124/pr.114.008862.

Langmead CJ, Christopoulos A. (2014)  Functional and structural perspectives on allosteric modulation of GPCRs.  Curr Opin Cell Biol 27:94-101. doi: 10.1016/j.ceb.2013.11.007

Langmead CJ, Christopoulos A. (2013) Supra-physiological .efficacy at GPCRs: superstition or super agonists?  Br J Pharmacol 169(2):353-6. doi: 10.1111/bph.12142.