Research Output

2013

Strategies to address low drug solubility in discovery and development

Williams, H. D., Trevaskis, N., Charman, S. A., Shanker, R., Charman, W. N., Pouton, C. W. & Porter, C. J., 2013, In : Pharmacological Reviews. 65, 1, p. 315 - 499 185 p.

Research output: Contribution to journalArticleResearchpeer-review

769 Citations (Scopus)

Structural and functional characterization of receptor kinases with nucleotide cyclase activity

Muleya, V., Wheeler, J. & Irving, H. R., 2013, Cyclic Nucleotide Signaling in Plants. Gehring, C. (ed.). USA: Humana Press, p. 175 - 194 20 p.

Research output: Chapter in Book/Report/Conference proceedingChapter (Book)Other

5 Citations (Scopus)

Structural basis for modulation of a G-protein-coupled receptor by allosteric drugs

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, In : Nature. 503, 7475, p. 295 - 299 5 p.

Research output: Contribution to journalArticleResearchpeer-review

268 Citations (Scopus)

Structural biology: meet the B family

Sexton, P. & Wootten, D. L., 2013, In : Nature. 499, 7459, p. 417 - 418 2 p.

Research output: Contribution to journalLetterOther

5 Citations (Scopus)

Structure-based ligand discovery targeting orthosteric and allosteric pockets of dopamine receptors

Lane, J. R. D., Chubukov, P., Liu, W., Canals, M., Cherezov, V., Abagyan, R., Stevens, R. C. & Katritch, V., 2013, In : Molecular Pharmacology. 84, 6, p. 794 - 807 14 p.

Research output: Contribution to journalArticleResearchpeer-review

61 Citations (Scopus)

Supra-physiological efficacy at GPCRs: superstition or super agonists?

Langmead, C. J. & Christopoulos, A., 2013, In : British Journal of Pharmacology. 169, 2, p. 353 - 356 4 p.

Research output: Contribution to journalArticleOtherpeer-review

20 Citations (Scopus)

Sympathetic nervous system regulation of metastasis

Pimentel, M., Chai, M. G., Le, C. P., Cole, S. W. & Sloan, E. K., 2013, Metastatic Cancer: Clinical and Biological Perspectives. Jandial, R. (ed.). Austin Texas USA: Landes Bioscience, p. 169 - 179 11 p.

Research output: Chapter in Book/Report/Conference proceedingChapter (Book)Researchpeer-review

Synthesis, functional and binding profile of (R)-apomorphine based homobivalent ligands targeting the dopamine D2 receptor

Shonberg, J., Lane, J. R. D., Scammells, P. J. & Capuano, B., 2013, In : MedChemComm. 4, 9, p. 1290 - 1296 7 p.

Research output: Contribution to journalArticleResearchpeer-review

6 Citations (Scopus)

The bile acid receptor TGR5 does not interact with b-arrestins or traffic to endosomes but transmits sustained signals from plasma membrane rafts

Jensen, D. D., Godfrey, C. B., Niklas, C., Canals, M., Kocan, M., Poole, D. P., Murphy, J. E., Alemi, F., Cottrell, G. S., Korbmacher, C., Lambert, N., Bunnett, N. W. & Corvera, C. U., 2013, In : The Journal of Biological Chemistry. 288, 32, p. 22942 - 22960 19 p.

Research output: Contribution to journalArticleResearchpeer-review

59 Citations (Scopus)

The receptor TGR5 mediates the prokinetic actions of intestinal bile acids and is required for normal defecation in mice

Alemi, F., Poole, D. P., Chiu, J. V., Schoonjans, K., Cattaruzza, F., Grider, J. R., Bunnett, N. W. & Corvera, C. U., 2013, In : Gastroenterology. 144, 1, p. 145 - 154 10 p.

Research output: Contribution to journalArticleResearchpeer-review

133 Citations (Scopus)

The TGR5 receptor mediates bile acid-induced itch and analgesia

Alemi, F., Kwon, E., Poole, D. P., Lieu, T. M., Lyo, V., Cattaruzza, F., Cevikbas, F., Steinhoff, M., Nassini, R., Materazzi, S., Guerrero-Alba, R., Valdez-Morales, E., Cottrell, G. S., Schoonjans, K., Geppetti, P., Vanner, S., Bunnett, N. W. & Corvera, C. U., 2013, In : Journal of Clinical Investigation. 123, 4, p. 1513 - 1530 18 p.

Research output: Contribution to journalArticleResearchpeer-review

Open Access
186 Citations (Scopus)

Toward the establishment of standardized in vitro tests for lipid-based formulations, part 3: Understanding supersaturation versus precipitation potential during the in vitro digestion of type I, II, IIIA, IIIB and IV lipid-based formulations

Williams, H. D., Sassene, P. J., Kleberg, K., Calderone, M., Igonin, A., Jule, E., Vertommen, J., Blundell, R., Benameur, H., Mullertz, A., Pouton, C. W. & Porter, C. J., 2013, In : Pharmaceutical Research. 30, 12, p. 3059 - 3076 18 p.

Research output: Contribution to journalArticleResearchpeer-review

69 Citations (Scopus)

Transient receptor potential ankyrin 1 mediates chronic pancreatitis pain in mice

Cattaruzza, F., Johnson, C., Leggit, A., Grady, E. F., Schenk, A. K., Cevikbas, F., Cedron, W., Bondada, S., Kirkwood, R., Malone, B., Steinhoff, M., Bunnett, N. W. & Kirkwood, K. S., 2013, In : American Journal of Physiology - Gastrointestinal and Liver Physiology. 304, 11, p. 1002 - 1012 11 p.

Research output: Contribution to journalArticleResearchpeer-review

26 Citations (Scopus)

Tyrosine sulfation of chemokine receptor CCR2 enhances interactions with both monomeric and dimeric forms of the chemokine monocyte chemoattractant protein-1 (MCP-1)

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, In : The Journal of Biological Chemistry. 288, 14, p. 10024 - 10034 11 p.

Research output: Contribution to journalArticleResearchpeer-review

55 Citations (Scopus)

Unique signaling profiles of positive allosteric modulators of metabotropic glutamate receptor subtype 5 determine differences in in vivo activity

Rook, J. M., Noetzel, M. J., Pouliot, W. A., Bridges, T. M., Vinson, P. N., Cho, H. P., Zhou, Y., Gogliotti, R. D., Manka, J. T., Gregory, K. J., Stauffer, S. R., Dudek, F. E., Xiang, Z., Niswender, C. M., Daniels, J. S., Jones, C. K., Lindsley, C. W. & Conn, P. J., 2013, In : Biological Psychiatry. 73, 6, p. 501 - 509 9 p.

Research output: Contribution to journalArticleResearchpeer-review

78 Citations (Scopus)
2012

Active cathepsins B, L, and S in murine and human pancreatitis

Lyo, V., Cattaruzza, F., Kim, T. N., Walker, A. W., Paulick, M., Cox, D. N., Cloyd, J., Buxbaum, J. L., Ostroff, J., Bogyo, M., Grady, E. F., Bunnett, N. W. & Kirkwood, K. S., 2012, In : American Journal of Physiology - Gastrointestinal and Liver Physiology. 303, 8, p. G894 - G903 10 p.

Research output: Contribution to journalArticleResearchpeer-review

20 Citations (Scopus)

Allosteric modulation of endogenous metabolites as an avenue for drug discovery

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, In : Molecular Pharmacology. 82, 2, p. 281 - 290 10 p.

Research output: Contribution to journalArticleResearchpeer-review

54 Citations (Scopus)

Allosteric modulation of seven transmembrane spanning receptors: theory, practice, and opportunities for central nervous system drug discovery

Melancon, B. J., Hopkins, C. R., Wood, M. R., Emmitte, K. A., Niswender, C. M., Christopoulos, A., Conn, P. J. & Lindsley, C. W., 2012, In : Journal of Medicinal Chemistry. 55, 4, p. 1445 - 1464 20 p.

Research output: Contribution to journalArticleResearchpeer-review

170 Citations (Scopus)

A Monod-Wyman-Changeux mechanism can explain G protein-coupled receptor (GPCR) allosteric modulation

Canals, M., Lane, J., Wen, A., Scammells, P., Sexton, P. & Christopoulos, A., 2012, In : The Journal of Biological Chemistry. 287, 1, p. 650 - 659 10 p.

Research output: Contribution to journalArticleResearchpeer-review

87 Citations (Scopus)

A simple method for quantifying functional selectivity and agonist bias

Kenakin, T., Watson, C., Muniz-Medina, V., Christopoulos, A. & Novick, S., 2012, In : ACS Chemical Neuroscience. 3, 3, p. 193 - 203 11 p.

Research output: Contribution to journalArticleResearchpeer-review

265 Citations (Scopus)

Beta(2)-adrenoceptors increase translocation of GLUT4 via GPCR kinase sites in the receptor C-terminal tail

Dehvari, N., Hutchinson, D., Nevzorova, J., Dallner, O., Sato, M., Kocan, M., Merlin, J., Evans, B., Summers, R. & Bengtsson, T., 2012, In : British Journal of Pharmacology. 165, 5, p. 1442 - 1456 15 p.

Research output: Contribution to journalArticleResearchpeer-review

18 Citations (Scopus)

Chemical subtleties in small-molecule modulation of peptide receptor function: the case of CXCR3 biaryl-type ligands

Wijtmans, M., Scholten, D. J., Roumen, L., Canals, M., Custers, H., Glas, M., Vreeker, M. C. A., De Kanter, F. J. J., de Graaf, C., Smit, M. J., de Esch, I. J. P. & Leurs, R., 13 Dec 2012, In : Journal of Medicinal Chemistry. 55, 23, p. 10572-10583 12 p.

Research output: Contribution to journalArticleResearchpeer-review

17 Citations (Scopus)

Consequences of splice variation on secretin family G protein-coupled receptor function

Furness, S. G. B., Wootten, D. L., Christopoulos, A. & Sexton, P. M., 2012, In : British Journal of Pharmacology. 166, 1, p. 98 - 109 12 p.

Research output: Contribution to journalArticleResearchpeer-review

Open Access
File
29 Citations (Scopus)

Design and receptor interactions of obligate dimeric mutant of chemokine monocyte chemoattractant protein-1 (MCP-1)

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, In : The Journal of Biological Chemistry. 287, 18, p. 14692 - 14702 11 p.

Research output: Contribution to journalArticleResearchpeer-review

36 Citations (Scopus)

Discovery of 2-(2-Benzoxazoyl amino)-4-aryl-5-cyanopyrimidine as negative allosteric modulators (NAMs) of metabotropic glutamate receptor 5 (mGlu 5): from an artificial neural network virtual screen to an in vivo tool compound

Mueller, R., Dawson, E. S., Meiler, J., Rodriguez, A. L., Chauder, B. A., Bates, B. S., Felts, A. S., Lamb, J. P., Menon, U. N., Jadhav, S. B., Kane, A. S., Jones, C. K., Gregory, K. J., Niswender, C. M., Conn, P. J., Olsen, C. M., Winder, D. G., Emmitte, K. A. & Lindsley, C. W., 2012, In : ChemMedChem. 7, 3, p. 406 - 414 9 p.

Research output: Contribution to journalArticleResearchpeer-review

31 Citations (Scopus)

Drug discovery and non-human kinomes

Wilks, A. F. & Lucet, I. S., 2012, Kinase Drug Discovery. Ward, R. A. & Goldberg, F. (eds.). 1st ed. UK: RSC Publishing, p. 262 - 285 24 p.

Research output: Chapter in Book/Report/Conference proceedingChapter (Book)Researchpeer-review

Fluorescent derivatives of AC-42 to probe bitopic orthosteric/allosteric binding mechanisms on muscarinic M1 receptors

Daval, S. B., Valant, C., Bonnet, D., Kellenberger, E., Hibert, M., Galzi, J-L. & Ilien, B., 2012, In : Journal of Medicinal Chemistry. 55, 5, p. 2125 - 2143 19 p.

Research output: Contribution to journalArticleResearchpeer-review

29 Citations (Scopus)

Glucagon-like peptide-1 receptor dimerization differentially regulates agonist signaling but does not affect small molecule allostery

Harikumar, K. G., Wootten, D. L., Pinon, D. I., Koole, C. R., Ball, A. M., Furness, S. GB., Graham, B., Dong, M., Christopoulos, A., Miller, L. J. & Sexton, P. M., 2012, In : Proceedings of the National Academy of Sciences of the United States of America. 109, 45, p. 18607 - 18612 6 p.

Research output: Contribution to journalArticleResearchpeer-review

Open Access
File
44 Citations (Scopus)

Homobivalent ligands of the atypical antipsychotic clozapine: Design, synthesis, and pharmacological evaluation

McRobb, F. M., Crosby, I. T., Yuriev, E., Lane, J. R. D. & Capuano, B., 2012, In : Journal of Medicinal Chemistry. 55, 4, p. 1622 - 1634 13 p.

Research output: Contribution to journalArticleResearchpeer-review

34 Citations (Scopus)

Identification of molecular phenotypes and biased signaling induced by naturally occurring mutations of the human calcium-sensing receptor

Leach, K., Wen, C., Davey, A. E., Sexton, P. M., Conigrave, A. D. & Christopoulos, A., 2012, In : Endocrinology. 153, 9, p. 4304 - 4316 13 p.

Research output: Contribution to journalArticleResearchpeer-review

52 Citations (Scopus)

Interaction with caveolin-1 modulates G protein coupling of the mouse beta3-adrenoceptor

Sato, M., Hutchinson, D. S., Halls, M. L., Furness, S. G. B., Bengtsson, T., Evans, B. A. & Summers, R. J., 2012, In : The Journal of Biological Chemistry. 287, 24, p. 20674 - 20688 15 p.

Research output: Contribution to journalArticleResearchpeer-review

Open Access
File
20 Citations (Scopus)

Investigating metabotropic glutamate receptor 5 allosteric modulator cooperativity, affinity, and agonism: Enriching structure-function studies and structure-activity relationships

Gregory, K. J., Noetzel, M. J., Rook, J. M., Vinson, P. N., Stauffer, S. R., Rodriguez, A. L., Emmitte, K. A., Zhou, Y., Chun, A. C., Felts, A. S., Chauder, B. A., Lindsley, C. W., Niswender, C. M. & Conn, P. J., 2012, In : Molecular Pharmacology. 82, 5, p. 860 - 875 16 p.

Research output: Contribution to journalArticleResearchpeer-review

65 Citations (Scopus)

Lifting the lid on GPCRs: the role of extracellular loops

Wheatley, M., Wootten, D. L., Conner, M., Simms, J. W., Kendrick, R., Logan, R. T., Poyner, D. R. & Barwell, J., 2012, In : British Journal of Pharmacology. 165, 6, p. 1688 - 1703 16 p.

Research output: Contribution to journalArticleResearchpeer-review

149 Citations (Scopus)

Ligand properties and behaviours in an allosteric age

Langmead, C. J., Dec 2012, In : Trends in Pharmacological Sciences. 33, 12, p. 621-622 2 p.

Research output: Contribution to journalLetterOtherpeer-review

5 Citations (Scopus)

Mapping spatial approximations between the amino terminus of secretin and each of the extracellular loops of its receptor using cysteine trapping

Dong, M., Xu, X., Ball, A. M., Makhoul, J. A., Lam, P. CH., Pinon, D. I., Orry, A., Sexton, P. M., Abagyan, R. & Miller, L. J., 2012, In : The FASEB Journal. 26, 12, p. 5092 - 5105 14 p.

Research output: Contribution to journalArticleResearchpeer-review

25 Citations (Scopus)

Mechanism of action of a nanomolar potent, allosteric antagonist of the thyroid-stimulating hormone receptor

van Koppen, C. J., de Gooyer, M. E., Karstens, W-J., Plate, R., Conti, P. G. M., van Achterberg, T. A. E., van Amstel, M. G. A., Brands, J. H. G. M., Wat, J., Berg, R. J. W., Lane, J. R. D., Miltenburg, A. M. M. & Timmers, C. M., 2012, In : British Journal of Pharmacology. 165, 7, p. 2314 - 2324 11 p.

Research output: Contribution to journalArticleResearchpeer-review

30 Citations (Scopus)

Minimization of human relaxin-3 leading to high-affinity analogues with increased selectivity for relaxin-family peptide 3 receptor (RXFP3) over RXFP1

Shabanpoor, F., Hossain, M. A., Ryan, P. J., Belgi, A., Layfield, S., Kocan, M., Zhang, S., Samuel, C. S., Gundlach, A. L., Bathgate, R. AD., Separovic, F. & Wade, J. D., 2012, In : Journal of Medicinal Chemistry. 55, 4, p. 1671 - 1681 11 p.

Research output: Contribution to journalArticleResearchpeer-review

62 Citations (Scopus)

Molecular basis for binding and subtype selectivity of 1,4-benzodiazepine antagonist ligands of the cholecystokinin receptor

Cawston, E. E., Lam, P. C. H., Harikumar, K. G., Dong, M., Ball, A. M., Augustine, M. L., Akgun, E., Portoghese, P. S., Orry, A., Abagyan, R., Sexton, P. M. & Miller, L., 2012, In : The Journal of Biological Chemistry. 287, 22, p. 18618 - 18635 18 p.

Research output: Contribution to journalArticleResearchpeer-review

15 Citations (Scopus)

Neurotensin-induced proinflammatory signaling in human colonocytes is regulated by beta-arrestins and endothelin-converting enzyme-1-dependent endocytosis and resensitization of neurotensin receptor 1

Law, I. K. M., Murphy, J. E., Bakirtzi, K., Bunnett, N. W. & Pothoulakis, C., 2012, In : The Journal of Biological Chemistry. 287, 18, p. 15066 - 15075 10 p.

Research output: Contribution to journalArticleResearchpeer-review

24 Citations (Scopus)

N-glycosylation determines ionic permeability and desensitization of the TRPV1 capsaicin receptor

Veldhuis, N. A., Lew, M. J., Abogadie, F. C., Poole, D. P., Jennings, E. A., Ivanusic, J. J., Eilers, H., Bunnett, N. W. & McIntyre, P. B., 2012, In : The Journal of Biological Chemistry. 287, 28, p. 21765 - 21772 8 p.

Research output: Contribution to journalArticleResearchpeer-review

35 Citations (Scopus)

Optimization of an ether series of mGlu5 positive allosteric modulators: molecular determinants of MPEP-site interaction crossover

Manka, J. T., Vinson, P. N., Gregory, K. J., Zhou, Y., Williams, R. E. A., Gogi, K., Days, E., Jadhav, S., Herman, E. J., Lavreysen, H., Mackie, C., Bartolome, J., Macdonald, G. J., Steckler, T., Daniels, J. S., Weaver, C. D., Niswender, C. M., Jones, C. K., Conn, P. J., Lindsley, C. W. & 1 others, Stauffer, S. R., 2012, In : Bioorganic and Medicinal Chemistry Letters. 22, 20, p. 6481 - 6485 5 p.

Research output: Contribution to journalArticleResearchpeer-review

11 Citations (Scopus)

Plasmodium kinases as targets for new-generation antimalarials

Lucet, I. S., Tobin, A., Drewry, D., Wilks, A. F. & Doerig, C. D., 2012, In : Future Medicinal Chemistry. 4, 18, p. 2295 - 2310 16 p.

Research output: Contribution to journalArticleResearchpeer-review

59 Citations (Scopus)
1 Citation (Scopus)

Positive and negative allosteric modulators promote biased signaling at the calcium-sensing receptor

Davey, A. E., Leach, K., Valant, C., Conigrave, A. D., Sexton, P. M. & Christopoulos, A., 2012, In : Endocrinology. 153, 3, p. 1232 - 1241 10 p.

Research output: Contribution to journalArticleResearchpeer-review

116 Citations (Scopus)

Preface

Fryer, A. D., Christopoulos, A. & Nathanson, N. M., 2012, Muscarinic Receptors. Vol. 208. (Handbook of Experimental Pharmacology; vol. 208).

Research output: Chapter in Book/Report/Conference proceedingForeword / PostscriptOtherpeer-review

84 Citations (Scopus)

Proteolytic activation of the epithelial sodium channel (ENaC) by the cysteine protease cathepsin-S

Haerteis, S., Krappitz, M., Bertog, M., Krappitz, A., Baraznenok, V. A., Henderson, I., Lindstrom, E., Murphy, J. E., Bunnett, N. W. & Korbmacher, C., 2012, In : Pflugers Archiv-European Journal of Physiology. 464, 4, p. 353 - 365 13 p.

Research output: Contribution to journalArticleResearchpeer-review

38 Citations (Scopus)