Ye Fang

..This study documents multiple ligand-specific states of the beta(2)-adrenoceptor and highlights the power of the biosensor assays for screening pathway-biased ligands...

..The roles of endocytosis and cytoskeleton modulation in B(2) signaling were also demonstrated...

..The present study is focused on the use of non-invasive and manipulation-free optical biosensors for assaying endogenous GPCRs in adherent cells...

..Assays to screen compounds for their pharmacological properties (binding affinity, relative potency and selectivity) using GPCR microarrays are discussed...

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..Integration of different ligand-binding assays is important to improve the efficiency of the drug discovery and development process...

..These challenges will need to be met for the wide adoption of these assays in drug discovery...

..This article reviews important advances in optical biosensor instrumentation, and highlights the potential of optical biosensors for drug discovery with an emphasis on whole cell sensing in both high throughput and high content fashions...

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..This article describes the uses of live cell optical sensing for probing cell biology and ligand pharmacology, with an emphasis of resonant waveguide grating biosensor cellular assays for high throughput applications...

..Protease activated receptors (PARs) consist of a family of four G protein-coupled receptors. Many types of cells express several PARs, whose physiological significance is mostly unknown...

..This article reviews the principles and potential of current label-free cell assay technologies in GPCR drug discovery...

..These results suggested that optical biosensors provide an attractive means to study the cytoskeleton structure and screen modulators that affect the cytoskeleton structure...

..This study provides fundamentals for probing living cells with the RWG biosensors, in general, optical biosensors...

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..The potential mechanisms and implications for the uses of air-stable GPCR microarrays were discussed...

..The DMR signals obtained serve as integrated signatures for interaction networks in the EGFR signaling...

..Assays to screen compounds for their pharmacological properties (binding affinity, relative potency and selectivity) using GPCR microarrays are discussed...

..Taken together, these features make the system ideally suited to explore the structure-activity relationship of compounds across a broad region of target class space...

..The bioassays and potential applications of GPCR microarrays for the determination of compound affinities and potencies are also included...

..Compound 13 was identified to the most potent GPR35 agonist, and compounds 30 and 36 exhibited the highest efficacy to cause β-arrestin translocation...

..Ligand binding selectivity and specificity to G protein-coupled receptor (GPCR) microarrays are presented. The potential applications of these arrays for drug screening are discussed...

..This study reveals the cellular mechanisms of agonist-selective β(2)AR desensitization at the whole cell level...

..These biosensor cellular assays hold the potential to reduce attrition rates in drug discovery and development process...

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..This study documents the integrative role of adenylyl cyclase in GPCR signaling and the power of forskolin as a pharmacological probe to differentiate receptor signaling using the label-free biosensor cellular assays...

..This study demonstrates that DMR assays can be used to elucidate the functional consequence of kinetics-driven antagonist occupancy in native cells...

..The present study provides novel chemical series as a starting point for further investigations of GPR35 biology and pharmacology...

..Such microarrays could potentially streamline drug discovery by helping integrate primary screening with selectivity and safety screening without compromising the essential functional information obtainable from cellular assays...

..These results not only suggest that D-luciferin is a partial agonist of GPR35, but also will evoke careful interpretation of biological data obtained using molecular and in vivo imaging assays when these probe molecules are used...

..These findings suggest that DMR assays can decode the differentiation process of stem cells at the cell system level...

..Results showed that ECM proteins had significant impacts on the DMR characteristics, potency, and efficacy of seven P2Y agonists. This study documents the importance of surface chemistry in regulating receptor signaling...

..Distinct optical signals could be generated with the pretreatment of the target cells with various known pharmaceutical reagents, making the assay useful for discovering new chemicals that may affect cell-cell communications...

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..These agonists provide pharmacological tools to study the biology and function of GPR35...

..This study demonstrates a new means to differentiate ligand-directed functional selectivity on trafficking of receptors...

..The chapter describes air-stable GPCR microarrays and their utility for selectivity profiling of GPCR drugs with high fidelity...

..GPR35 may represent a target for the treatment of allergic disorders including asthma...

..Salicyluric acid, the main metabolite of aspirin, was also active. These results suggest that the GPR35 agonist activity of certain aspirin metabolites may contribute to the clinical features of aspirin...

..This first ever demonstration of direct pin-printing of membrane proteins and ligand-binding assays thereof fills a significant void in protein microchip technology--the lack of practical microarray-based methods for membrane proteins...

..These results suggest that multiple tyrosine metabolites are alternative endogenous ligands of GPR35, and GPR35 may represent a druggable target for treating certain diseases associated with abnormality of tyrosine metabolism...

..We demonstrate that the approach establishes an effective link between the label-free pharmacology and in vivo therapeutic indications of drugs...

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..The Epic DMR technology provides a generic platform amenable to pharmacological evaluation of cellular responses to GPCR activation in a label-free live cell assay format...

..The impact of this approach on screening in drug discovery is discussed...