Ligand-receptor interaction platforms and their applications for drug discovery

Expert Opinion on Drug Discovery

Volumn 7, Issue 10, 2012, Pages 969-988

  Fang, Ye ^a  

^a Science and Technology Division   (United States)

Author keywords

Affinity; Backscattering interferometry; Biochemical mechanism of action; Biolayer interferometry; Calorimetry; Conformation; Crystallography; Drugtarget interaction; Fluorescence; in silico screening; Kinetics; Label free; Ligand binding techniques; Microfluidics; Nuclear magnetic resonance; Plasmon waveguide resonance; Polypharmacology; Protein thermal denaturation; Radioligand binding; Rebinding; Residence time; Resonant waveguide grating; Surface acoustic wave; Surface plasmon resonance; Thermodynamics; Whispering gallery mode

Indexed keywords

ADRENALIN; CANDESARTAN; CARAZOLOL; CLOZAPINE; FLUORESCENT DYE; ISOPRENALINE; NEUROLEPTIC AGENT; QUETIAPINE; RADIOLIGAND; SALMETEROL; SPIPERONE; TIOTROPIUM BROMIDE;

BACKSCATTERING INTERFEROMETRY; BINDING AFFINITY; BINDING ASSAY; BINDING KINETICS; BIOSENSOR; CARDIOVASCULAR DISEASE; CHEMICAL ANALYSIS; DRUG CONFORMATION; DRUG EFFICACY; DRUG RECEPTOR BINDING; DRUG TARGETING; FLUORESCENCE; HUMAN; IMAGING; INTERFEROMETRY; INTERFEROMETRY BIOSENSOR; ISOTHERMAL TITRATION CALORIMETRY; LIGAND BINDING; MEAN RESIDENCE TIME; MICROFLUIDICS; MOLECULAR PROBE; NONHUMAN; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PARKINSONISM; PRIORITY JOURNAL; PROTEIN DENATURATION; PROTEIN INTERACTION; PSYCHOSIS; RADIOASSAY; RESONANT WAVEGUIDE GRATING; REVIEW; SURFACE ACOUSTIC WAVE BIOSENSOR; SURFACE PLASMON RESONANCE; TARDIVE DYSKINESIA; THERMAL DENATURATION ASSAY; THERMODYNAMICS; WHISPERING GALLERY MICRORESONATOR; X RAY CRYSTALLOGRAPHY;

ANIMALS; DRUG DISCOVERY; HUMANS; LIGANDS; PHARMACEUTICAL PREPARATIONS; PROTEIN BINDING; RADIOLIGAND ASSAY;

EID: 84866875777     PISSN: 17460441     EISSN: 1746045X     Source Type: Journal    
DOI: 10.1517/17460441.2012.715631     Document Type: Review

References (182)

1. Hopkins AL, Groom CR. The druggable genome. Nat Rev Drug Discov 2002;1:727-30
2. Yildirim MA, Goh KI, Cusick ME, et al. Drug-target network. Nat Biotechnol 2007;25:1119-26
3. Wurm FM. Production of recombinant protein therapeutics in cultivated mammalian cells. Nat Biotechnol 2004;22:1393-8
4. Khan MN, Findlay JWA. editors. Ligand-binding assays: development, validation, and implementation in the drug development arena. John Wiley & Sons; Hoboken, NJ, USA: 2009
5. Nunez S, Venhorst J, Kruse CG. Target-drug interactions: first principles and their application to drug discovery. Drug Discov Today 2012;17:10-22
6. Gleeson M, Hersey A, Montanari D, Overington J. Probing the links between in vitro potency, ADMET and physicochemical parameters. Nat Rev Drug Discov 2011;10:197-208
7. Copeland RA, Pompliano DL, Meek TD. Drug-target residence time and its implications for lead optimization. Nat Rev Drug Discov 2006;5:730-9
8. Mailman RB. GPCR functional selectivity has therapeutic impact. Trends Pharmacol Sci 2007;28:390-6
9. Kenakin T, Miller LJ. Seven transmembrane receptors as shapeshifting proteins: the impact of allosteric modulation and functional selectivity on new drug discovery. Pharmacol Rev 2010;62:265-304
10. Kinzer-Ursem TL, Linderman JJ. Both ligand- and cell-specific parameters control ligand agonism in a kinetic model of G protein-coupled receptor signaling. PLoS Comput Biol 2007;3:e6
11. Kenakin T. Being mindful of seven-transmembrane receptor 'guests' when assessing agonist selectivity. Br J Pharmacol 2010;160:1045-7
12. Birdsall NJ, Hulme EC, Burgen A. The character of the muscarinic receptors in different regions of the rat brain. Proc R Soc Lond B Biol Sci 1980;207:1-12
13. Boehr DD, Nussinov R, Wright PE. The role of dynamic conformational ensembles in biomolecular recognition. Nat Chem Biol 2009;5:789-96
14. Rosenbaum DM, Rasmussen SG, Kobilka BK. The structure and function of G-protein-coupled receptors. Nature 2009;459:356-63
15. Dror RO, Pan AC, Arlow DH, et al. Pathway and mechanism of drug binding to G-protein-coupled receptors. Proc Natl Acad Sci USA 2011;108:13118-23
16. Kolb P, Rosenbaum DM, Irwin JJ, et al. Structure-based discovery of b2-adrenergic receptor ligands. Proc Natl Acad Sci USA 2009;106:6843-8
17. Pammolli F, Magazzini L, Riccaboni M. The productivity crisis in pharmaceutical R&D. Nat Rev Drug Discov 2011;10:428-38
18. Swinney DC. Biochemical mechanisms of drug action: what does it take for success? Nat Rev Drug Discov 2004;3:801-8
19. Tummina PJ, Copeland RA. Residence time of receptor-ligand complexes and its effect on biological functions. Biochemistry 2008;47:5481-92
20. Zhang R, Monsma F. The importance of drug-target residence time. Curr Opin Drug Discov Devel 2009;12:488-96
21. Copeland RA. The dynamics of drug-target interactions: drug-target residence time and its impact on efficacy and safety. Expert Opin Drug Discov 2010;5:305-10
22. Lu H, Tonge PJ. Drug-target residence time: critical information for lead optimization. Curr Opin Chem Biol 2010;14:467-74
23. Zhang R, Monsma F. Binding kinetics and mechanism of action: toward the discovery and development of better and best in class drugs. Expert Opin Drug Discov 2010;5:1023-9
24. Singh J, Petter RC, Baillie TA, Whitty A. The resurgence of covalent drugs. Nat Rev Drug Discov 2011;10:307-17
25. Disse B, Speck GA, Rominger KL, et al. Tiotropium (Spiriva): mechanistical considerations and clinical profile in obstructive lung disease. Life Sci 1999;64:457-64
26. Barnes PJ. The pharmacological properties of tiotropium. Chest 2000;117:63S-6S
27. Kapur S, Seeman P. Does fast dissociation from the dopamine D2 receptor explain the action of atypical antipsychotics? A new hypothesis. Am J Psychiatry 2001;158:360-9
28. Dokoumetzidis A, Karalis V, Iliadis A, Macheras P. The heterogeneous course of drug transit through the body. Trends Pharmacol Sci 2004;25:140-6
29. Coombs D, Goldstein B. Effects of geometry of the immunological synapse on the delivery of effector molecules. Biophys J 2004;87:2215-20
30. Vauquelin G, Charlton SJ. Long-acting target binding and rebinding as mechanisms to prolong in vivo drug action. Br J Pharmacol 2010;161:488-508
31. Karlsson R, Falt R. Experimental design for the kinetic analysis of protein-protein interactions with surface plasmon resonance biosensors. J Immunol Method 1997;200:121-33
32. Bissantz C, Kuhn B, Stahl M. A medicinal chemist's guide to molecular interactions. J Med Chem 2010;53:5061-84
33. Whitesides GM, Krishnamurthy VM. Designing ligands to bind proteins. Q. Rev. Biophys 2005;38:385-95
34. Ferenczy GG, Keseru GM. Thermodynamics guided lead discovery and optimization. Drug Discov Today 2010;15:919-32
35. Hopkins AL, Groom CR, Alex A. Ligand efficiency: a useful metric for lead selection. Drug Discov Today 2004;9:430-1
36. Kuntz ID, Chen K, Sharp KA, Kollman PA. The maximal affinity of ligands. Proc Natl Acad Sci USA 1999;96:9997-10002
37. Abad-Zapatero C, Metz JT. Ligand efficiency indices as guideposts for drug discovery. Drug Discov Today 2005;10:464-9
38. Abad-Zapatero C. Ligand efficiency indices for effective drug discovery. Expert Opin Drug Discov 2007;2:469-88
39. Abad-Zapatero C, Perisic O, Wass J, et al. Ligand efficiency indices for an effective mapping of chemico-biological space: the concept of an atlas-like representation. Drug Discov Today 2010;15:804-11
40. Holdgate GA. Kinetic efficiency: the missing metric for enhancing compound quality? Drug Discov Today 2011;16:910-13
41. Leeson PD, Springthorpe B. The influence of drug-like concepts on decision-making in medicinal chemistry. Nat Rev Drug Discov 2007;6:881-90
42. Reynolds CH, Tounge BA, Bembenek SD. Ligand binding efficiency: trends, physical basis, and implications. J Med Chem 2008;51:2432-8
43. Bembenek SD, Tounge BA, Reynolds CH. Ligand efficiency and fragment-based drug discovery. Drug Discov Today 2009;14:278-83
44. Nissink JWM. Simple size-independent measure of ligand efficiency. J Chem Inf Model 2009;49:1617-22
45. Schultes S, de Graff C, Haaksma EEJ, et al. Ligand efficiency as a guide in fragment hit selection and optimization. Drug Discov Today Technol 2010;7:e157
46. Keen M. Receptor binding techniques. Methods Mol Biol 1999;106:1-290
47. Glickman JF, Schmid A, Ferrand S. Scintillation proximity assays in high-throughput screening. Assay Drug Dev Technol 2008;6:433-55
48. Hulme EC, Trevethick MA. Ligand binding assays at equilibrium: validation and interpretation. Br J Pharmacol 2010;161:1219-37
49. Vauquelin G. Determination of drug-receptor residence times by radioligand binding and functional assays: experimental strategies and physiological relevance. Med Chem Commun 2012;3:645-51
50. Owicki JC. Fluorescence polarization and anisotropy in high throughput screening: perspectives and primer. J Biomol Screen 2000;5:297-306
51. Handl HL, Gillies RJ. Lanthanide-based luminescent assays for ligand-receptor interactions. Life Sci 2005;77:361-71
52. Lea WA, Simeonov A. Fluorescence polarization assays in small molecule screening. Expert Opin Drug Discov 2011;6:17-32
53. Rossi AM, Taylor CW. Analysis of protein-ligand interactions by fluorescence polarization. Nat Protoc 2011;6:365-87
54. Lohse MJ, Nuber S, Hoffmann C. Fluorescence/bioluminescence resonance energy transfer techniques to study G-protein-coupled receptor activation and signaling. Pharmacol Rev 2012;64:299-336
55. Lieto AM, Cush RC, Thompson NL. Ligand-receptor kinetics measured by total internal reflection with fluorescence correlation spectroscopy. Biophys J 2003;85:3294-302
56. Sundberg SA. High-throughput and ultra-high-throughput screening: solution- and cell-based approaches. Curr Opin Biotechnol 2000;11:47-53
57. Ma H, Deacon S, Horiuchi K. The challenge of selecting protein kinase assays for lead discovery optimization. Expert Opin Drug Discov 2008;3:607-21
58. Simard JR, Rauh D. Fluorescence labels in kinases: a high-throughput kinase binding assay for the identification of DFG-out binding ligands. Methods Mol Biol 2012;800:95-117
59. Hemmila IA, Hurskainen P. Novel detection strategies for drug discovery. Drug Discov Today 2002;7:150-6
60. Hu H, Deng H, Fang Y. Label-free phenotypic profiling identified D-luciferin as a GPR35 agonist. PLoS One 2012;7:e34934
61. Zhu H, Bilgin M, Bangham R, et al. Global analysis of protein activities using proteome chips. Science 2001;293:2101-5
62. Fang Y, Lahiri J, Picard L. G protein-coupled receptor microarrays for drug discovery. Drug Discov Today 2003;8:755-61
63. LaBaer J, Ramachandran N. Protein microarrays as tools for functional proteomics. Curr Opin Chem Biol 2005;9:14-19
64. Li T, Liu D, Wang Z. Screening kinase inhibitors with a microarray-based fluorescent and resonance light scattering assay. Anal Chem 2010;82:3067-72
65. Fang Y, Peng J, Ferrie AM, Burkhalter RS. Air-stable G protein-coupled receptor microarrays and ligand binding characteristics. Anal Chem 2006;78:149-55
66. Ritchie RH. Plasma losses by fast electrons in thin films. Phys Rev 1957;106:874-81
67. Daghestani HN, Day BW. Theory and applications of surface plasmon resonance, resonant mirror, resonant waveguide grating, and dual polarization interferometry biosensors. Sensors 2010;10:9630-46
68. Liedberg B, Nylander C, Lundstrom I. Biosensing with surface plasmon resonance - how it all started. Biosens Bioelectron 1995;10:i-ix
69. Rich RL, Myszka DG. Advances in surface plasmon resonance biosensor analysis. Curr Opin Biotechnol 2000;11:54-61
70. Rich RL, Myszka DG. Higherthroughput, label-free, real-time molecular interaction analysis. Anal Biochem 2007;361:1-6
71. Rich RL, Myszka DG. Survey of the year 2006 commercial optical biosensor literature. J Mol Recognit 2006;20:300-66
72. Bieri C, Ernst OP, Heyse S, et al. Micropatterned immobilization of a G protein-coupled receptor and direct detection of G protein activation. Nat Biotechnol 1999;17:1105-8
73. Navratilova I, Besnard J, Hopkins AL. Screening for GPCR ligands using surface plasmon resonance. ACS Med Chem Lett 2011;2:549-54
74. Tollin G, Salamon Z, Hruby VJ. Techniques: plasmon-waveguide resonance (PWR) spectroscopy as a tool to study ligand-GPCR interactions. Trends Pharmacol Sci 2003;24:655-9
75. Salamon Z, Tollin G. Graphical analysis of mass and anisotropy changes observed by plasmon-waveguide resonance spectroscopy can provide useful insights into membrane protein function. Biophys J 2004;86:2508-16
76. Alves ID, Cowell SM, Salamon Z, et al. Different structural states of the proteolipid membrane are produced by ligand binding to the human -opioid receptor as shown by plasmon-waveguide resonance spectroscopy. Mol Pharmacol 2004;65:1248-57
77. Fang Y. Non-invasive optical biosensor for probing cell signaling. Sensors 2007;7:2316-29
78. Cunningham B, Li P, Lin B, Pepper J. Colorimetric resonant reflection as a direct biochemical assay technique. Sensors Actuators B Chem 2002;81:316-28
79. Wu M, Coblitz B, Shikano S, et al. Phospho-specific recognition by 14-3-3 proteins and antibodies monitored by a high throughput label-free optical biosensor. FEBS Lett 2006;580:5681-9
80. Heeres JT, Hergenrother PJ. High-throughput screening for modulators of protein-protein interactions: use of photonic crystal biosensors and complementary technologies. Chem Soc Rev 2011;40:4398-410
81. Wells CA, Betke KM, Lindsley CW, Hamm HE. Label-free detection of G protein-SNARE interactions and screening for small molecule modulators. ACS Chem Neurosci 2012;3:69-78
82. Geschwindner S, Carlsson JF, Knecht W. Application of optical biosensors in small-molecule screening activities. Sensors 2012;12:4311-23
83. Nirschl M, Reuter F, Voros J. Review of transducer principles for label-free biomolecular interaction analysis. Biosensors 2011;1:70-92
84. Concepcion J, Witte K, Wartchow C, et al. Label-free detection of biomolecular interactions using BioLayer interferometry for kinetic characterization. Comb Chem High Throughput Screen 2009;12:791-800
85. Wartchow CA, Podlaski F, Li S, et al. Biosensor-based small molecule fragment screening with biolayer interferometry. J Comput Aided Mol Des 2011;25:669-76
86. Scarano S, Mascini M, Turner APF, Minunni M. Surface plasmon resonance imaging for affinity-based biosensors. Biosens Bioelectron 2010;25:957-66
87. Bally M, Halter M, Voros J, Grandin HM. Optical microarray biosensing techniques. Surf Interface Anal 2006;38:1442-58
88. Rich RL, Miles AR, Gale BK, Myszka DG. Detergent screening of a G-protein-coupled receptor using serial and array biosensor technologies. Anal Biochem 2009;386:98-104
89. Ramachandran N, Larson DN, Stark PR, Hainsworth E. Emerging tools for real-time label-free detection of interactions on functional protein microarrays. FEBS J 2005;272:5412-25
90. Boozer C, Kim G, Cong S, et al. Looking towards label-free biomolecular interaction analysis in a high-throughput format: a review of new surface plasmon resonance technologies. Curr Opin Biotechnol 2006;17:400-5
91. Lausted C, Hu Z, Hood L. Quantitative serum proteomics from surface plasmon resonance imaging. Mol Cell Proteomics 2008;7:2464-74
92. Smith EA, Thomas WD, Kiessling LL, Corn RM. Surface plasmon resonance imaging studies of protein-carbohydrate interactions. J Am Chem Soc 2003;125:6140-8
93. Nedelkov D. Development of a surface plasmon resonance mass spectrometry array platform. Anal Chem 2007;79:5987-90
94. Li Y, Lee HJ, Corn RM. Fabrication and characterization of RNA aptamer microarrays for the study of protein-aptamer interactions with SPR imaging. Nucleic Acids Res 2006;34:6416-24
95. Fang S, Lee HJ, Wark AW, Corn RM. Attomole detection of microRNAs by nanoparticle-amplified SPR imaging measurements of surface polyadenylation reactions. J Am Chem Soc 2006;128:14044-6
96. Blow N. Proteins and proteomics: life on the surface. Nat Methods 2009;6:389-93
97. Vollmer F, Braun D, Libchaber A, et al. Protein detection by optical shift of a resonant microcavity. Appl Phys Lett 2002;80:4057-9
98. Arnold S, Khoshsima M, Teraoka I, et al. Shift of whispering-gallery modes in microspheres by protein adsorption. Opt Lett 2003;28:272-4
99. Topolancik J, Vollmer F. Photoinduced transformations in bacteriorhodopsin membrane monitored with optical microcavities. Biophys J 2007;92:2223-9
100. Vollmer F, Arnold S, Keng D. Single virus detection from the reactive shift, of a whispering-gallery mode. Proc Natl Acad Sci USA 2008;105:20701-4
101. Vollmer F, Arnold S. Whispering-gallery-mode biosensing: label-free detection down to single molecules. Nat Methods 2008;5:591-6
102. Armani AM, Kulkarni RP, Fraser SE, et al. Label-free, single-molecule detection with optical microcavities. Science 2007;317:783-7
103. Mazur B, Mertas A, Son'ta-Jakimczyk D, et al. Concentration of IL-2, IL-6, IL-8, IL-10 and TNF-alpha in children with acute lymphoblastic leukemia after cessation of chemotherapy. Hematol Oncol 2004;22:27-34
104. Dominguez-Juarez JL, Kozyreff G, Martorell J. Whispering gallery microresonators for second harmonic light generation from a low number of small molecules. Nat Commun 2011;2:254
105. Bornhop DJ, Latham JC, Kussrow A, et al. Free-solution, label-free molecular interactions studied by back-scattering interferometry. Science 2007;317:1732-6
106. Latham JC, Stein RA, Bornhop DJ, Mchaourab HS. Free-solution label-free detection of alpha-crystallin chaperone interactions by back-scattering interferometry. Anal Chem 2009;81:1865-71
107. Morcos EF, Kussrow A, Enders C, Bornhop D. Free-solution interaction assay of carbonic anhydrase to its inhibitors using back-scattering interferometry. Electrophoresis 2010;31:3691-5
108. Baksh MM, Kussrow AK, Mileni M, et al. Label-free quantification of membrane-ligand interactions using backscattering interferometry. Nat Biotechnol 2011;29:357-60
109. Fang Y, Frutos A, Lahiri J. Ganglioside Microarrays for Toxin Detection. Langmuir 2003;19:1500
110. Torres FE, Recht MI, Coyle JE, et al. Higher throughput calorimetry: opportunities, approaches and challenges. Curr Opin Struct Biol 2010;20:598-605
111. Niesen FH, Berglund H, Vedadi M. The use of differential scanning fluorimetry to detect ligand interactions that promote protein stability. Nat Protoc 2007;2:2212-21
112. Senisterra GA, Markin E, Yamazaki K, et al. Screening for ligands using a generic and high-throughput light-scattering-based assay. J Biomol Screen 2006;11:940-8
113. Vedadi M, Niesen FH, Allali-Hassani A, et al. Chemical screening methods to identify ligands that promote protein stability, protein crystallization, and structure determination. Proc Natl Acad Sci USA 2006;103:15835-40
114. Senisterra G, Chau I, Vedadi M. Thermal denaturation assays in chemical biology. Assay Drug Dev Technol 2012;10:128-36
115. Williams SP, Kuyper LF, Pearce KH. Recent applications of protein crystallography and structure-guided drug design. Curr Opin Chem Biol 2005;9:371-80
116. Blundell TL, Jhoti H, Abell C. High-throughput crystallography for lead discovery in drug design. Nat Rev Drug Discov 2002;1:45-54
117. Lyne PD. Structure-based virtual screening: an overview. Drug Discov Today 2002;7:1047-55
118. Kitchen DB, Decornez H, Furr JR, Bajorath J. Docking and scoring in virtual screening for drug discovery: methods and applications. Nat Rev Drug Discov 2004;3:935-49
119. Irwin JJ, Shoichet BK. ZINC - a free database of commercially available compounds for virtual screening. J Chem Inf Model 2005;45:177-82
120. Shoichet BK. Virtual screening of chemical libraries. Nature 2004;432:862-5
121. Pellecchia M, Sem DS, Wuthrich K. NMR in drug discovery. Nat Rev Drug Discov 2002;1:211-19
122. Pellecchia M, Bertini I, Cowburn D, et al. Perspectives on NMR in drug discovery: a technique comes of age. Nat Rev Drug Discov 2008;7:738-45
123. Dalvit C. NMR methods in fragment screening: theory and a comparison with other biophysical techniques. Drug Discov Today 2009;14:1051-7
124. Palczewski K, Kumasaka T, Hori T, et al. Crystal structure of rhodopsin: a G protein-coupled receptor. Science 2000;289:739-45
125. Rasmussen SG, Choi HJ, Rosenbaum DM, et al. Crystal structure of the human b2 adrenergic G-protein-coupled receptor. Nature 2007;450:383-7
126. Warne T, Serrano-Vega MJ, Baker JG, et al. Structure of b1-adrenergic G-protein-coupled receptor. Nature 2008;454:486-91
127. Jaakola VP, Griffith MT, Hanson MA, et al. The 2.6 angstrom crystal structure of a human A2A adenosine receptor bound to an antagonist. Science 2008;322:1211-17
128. Wu B, Chien EY, Mol CD, et al. Structures of the CXCR4 chemokine GPCR with small-molecule and cyclic peptide antagonists. Science 2010;330:1066-71
129. Chien EY, Liu W, Zhao Q, et al. Structure of the human dopamine D3 receptor in complex with a D2/D3 selective antagonist. Science 2010;330:1091-5
130. Shimamura T, Shiroishi M, Weyand S, et al. Structure of the human histamine H1 receptor complex with doxepin. Nature 2011;475:65-70
131. Hanson MA, Roth CB, Jo E, et al. Crystal structure of a lipid G protein-coupled receptor. Science 2012;335:851-5
132. Kruse AC, Hu J, Pan AC, et al. Structure and dynamics of the M3 muscarinic acetylcholine receptor. Nature 2012;482:552-6
133. Haga K, Kruse AC, Asada H, et al. Structure of the human M2 muscarinic acetylcholine receptor bound to an antagonist. Nature 2012;482:547-51
134. Wu H, Wacker D, Mileni M, et al. Structure of the human k-opioid receptor in complex with JDTic. Nature 2012;485:327-32
135. Manglik A, Kruse AC, Kobilka TS, et al. Crystal structure of the μ-opioid receptor bound to a morphine antagonist. Nature 2012;485:321-6
136. Thompson AA, Liu W, Chun E, et al. Structure of the nociceptin/orphanin FQ receptor in complex with a peptide mimetic. Nature 2012;485:395-9
137. Granier S, Manglik A, Kruse AC, et al. Structure of the d-opioid receptor bound to naltrindole. Nature 2012;485:400-4
138. Rasmussen SG, DeVree BT, Zou Y, et al. Crystal structure of the b2 adrenergic receptor-Gs protein complex. Nature 2011;477:549-55
139. Carlsson J, Yoo L, Gao ZG, et al. Structure-based discovery of A2A adenosine receptor ligands. J Med Chem 2010;53:3748-55
140. Carlsson J, Coleman RG, Setola V, et al. Ligand discovery from a dopamine D3 receptor homology model and crystal structure. Nat Chem Biol 2011;7:769-78
141. Mysinger MM, Weiss DR, Ziarek JJ, et al. Structure-based ligand discovery for the protein-protein interface of chemokine receptor CXCR4. Proc Natl Acad Sci USA 2012;109:5517-22
142. Rocha-Gaso MI, March-Iborra C, Montoya-Baides A, Arnau-Vives A. Surface generated acoustic wave biosensors for the detection of pathogens: a review. Sensors 2009;9:5740-69
143. Länge K, Rapp BE, Rapp M. Surface acoustic wave biosensors: a review. Anal Bioanal Chem 2008;391:1509-19
144. Fang Y, Ferrie AM, Li G. Probing cytoskeleton modulation by optical biosensors. FEBS Lett 2005;579:4175-80
145. Fang Y, Ferrie AM, Fontaine NH, Yuen PK. Characteristics of dynamic mass redistribution of EGF receptor signaling in living cells measured with label free optical biosensors. Anal Chem 2005;77:5720-5
146. Fang Y, Li G, Peng J. Optical biosensor provides insights for bradykinin B2 receptor signaling in A431 cells. FEBS Lett 2005;579:6365-74
147. Fang Y, Ferrie AM, Fontaine NH, et al. Resonant waveguide grating biosensor for living cell sensing. Biophys J 2006;91:1925-40
148. Fang Y, Li G, Ferrie AM. Non-invasive optical biosensor for assaying endogenous G protein-coupled receptors in adherent cells. J Pharamcol Toxicol Methods 2007;55:314-22
149. Fang Y, Ferrie AM. Label-free optical biosensor for ligand-directed functional selectivity of acting on b2 adrenoceptor in living cells. FEBS Lett 2008;582:558-64
150. Deng H, Hu H, Fang Y. Tyrphostin analogs are GPR35 agonists. FEBS Lett 2011;585:1957-62
151. Verrier F, An S, Ferrie AM, et al. GPCRs regulate the assembly of a multienzyme complex for purine biosynthesis. Nat Chem Biol 2011;7:909-15
152. Fang Y. Label-free receptor assays. Drug Discov Today Technol 2010;7:e5-e11
153. Fang Y. The development of label-free cellular assays for drug discovery. Expert Opin Drug Discov 2011;6:1285-98
154. Schroeder R, Merten N, Mathiesen JM, et al. The C-terminal tail of CRTH2 is a key molecular determinant that constrains Gi- and downstream-signaling cascade activation. J Biol Chem 2009;284:1324-36
155. Owens RM, Wang C, You JA, et al. Real-time quantitation of viral replication and inhibitor potency using a label-free optical biosensor. J Recept Signal Transduct Res 2009;29:195-201
156. Kebig A, Kostenis E, Mohr K, Mohr-Andr M. An optical dynamic mass redistribution assay reveals biased signaling of dualsteric GPCR activators. J Recept Signal Transduct Res 2009;29:140-5
157. Schröder R, Janssen N, Schmidt J, et al. Deconvolution of complex G protein-coupled receptor signaling in live cells using dynamic mass redistribution measurements. Nat Biotechnol 2010;28:943-9
158. Codd EE, Mabus JR, Murray BS, et al. Dynamic mass redistribution as a means to measure and differentiate signaling via opioid and cannabinoid receptors. Assay Drug Dev Technol 2011;9:362-72
159. Wong SH, Gao A, Ward S, et al. Development of a label-free assay for sodium-dependent phosphate transporter NaPi-IIb. J Biomol Screen 2012;17:829-34
160. Watson SJ, Brown AJ, Holliday ND. Differential signaling by splice variants of the human free fatty acid receptor GPR120. Mol Pharmacol 2012;81:631-42
161. Tran E, Sun H, Fang Y. Dynamic mass redistribution assays decodes surface influence on signaling of endogenous purinergic receptors. Assays Drug Dev Technol 2012;10:37-45
162. Goral V, Jin Y, Sun H, et al. Agonist-directed desensitization of the b2-adrenergic receptor. PLoS One 2011;6:e19282
163. Goral V, Wu Q, Sun H, Fang Y. Label-free optical biosensor with microfluidics for sensing ligand-directed functional selectivity on trafficking of thrombin receptor. FEBS Lett 2011;585:1054-60
164. Zaytseva N, Miller W, Goral V, et al. Microfluidic resonant waveguide grating biosensor system for whole cell sensing. Appl Phys Lett 2011;96:163703
165. Ferrie AM, Wu Q, Fang Y. Resonant waveguide grating imager for live cell sensing. Appl Phys Lett 2010;97:223704
166. Ferrie AM, Deichmann OD, Wu Q, Fang Y. High resolution resonant waveguide grating imager for cell cluster analysis under physiological condition. Appl Phys Lett 2012;100:223701
167. Congreve M, Andrews SP, Doré AS, et al. Discovery of 1,2,4-triazine derivatives as adenosine A2A antagonists using structure based drug design. J Med Chem 2012;55:1898-903
168. Teague SJ. Learning lessons from drugs that have recently entered the market. Drug Discov Today 2011;16:398-411
169. Miller DC, Lunn G, Jones P, et al. Investigation of the effect of molecular properties on the binding kinetics of a ligand to its biological target. Med Chem Commun 2012;3:449-52
170. Keiser MJ, Irwin JJ, Shoichet BK. The chemical basis of pharmacology. Biochemistry 2010;49:10267-76
171. Vieth M, Siegel MG, Higgs RE, et al. Characteristic physical properties and structural fragments of marketed oral drugs. J Med Chem 2004;47:224-32
172. Rees DC, Congreve M, Murray CW, Carr R. Fragment-based lead discovery. Nat Rev Drug Discov 2004;5:660-72
173. Chene P. Can biochemistry drive drug discovery beyond simple potency measurements? Drug Discov Today 2012;17:388-95
174. Keighley W. The need for high throughput kinetics early in the drug discovery process. Drug Discov World 2011;12(3):39-45
175. Hopkins AL. Network pharmacology: the next paradigm in drug discovery. Nat Chem Biol 2008;4:682-90
176. Campillos M, Kuhn M, Gavin AC, et al. Drug target identification using side-effect similarity. Science 2008;321:263-6
177. Keiser MJ, Setola V, Irwin JJ, et al. Predicting new molecular targets for known drugs. Nature 2009;462:175-81
178. Milletti F, Vulpetti A. Predicting polypharmacology by binding site similarity: from kinetics to the protein universe. J Chem Inf Model 2010;50:1418-31
179. Fliri AF, Loging WT, Thadeio PF, Volkmann RA. Biological spectra analysis: linking biological activity profiles to molecular structures. Proc Natl Acad Sci USA 2005;102:261-6
180. Anastassiadis T, Deacon SW, Devarajan K, et al. Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. Nat Biotechnol 2011;29:1039-45
181. Davis MI, Hunt JP, Herrgard S, et al. Comprehensive analysis of kinase inhibitor selectivity. Nat Biotechnol 2011;29:1046-51
182. Apsel B, Blair JA, Gonzalez B, et al. Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases. Nat Chem Biol 2008;4:691-9