Development of a Plate-Based Optical Biosensor Fragment Screening Methodology to Identify Phosphodiesterase 10A Inhibitors
We describe the development of a novel fragment screening methodology employing a plate-based optical biosensor system that can operate in a 384-well format. The method is based on the “inhibition in solution assay” (ISA) approach using an immobilized target definition compound (TDC) that has been s...
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| Veröffentlicht in: | Journal of medicinal chemistry 2013-04, Vol.56 (8), p.3228-3234 |
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| container_issue | 8 |
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| container_title | Journal of medicinal chemistry |
| container_volume | 56 |
| creator | Geschwindner, Stefan Dekker, Niek Horsefield, Rob Tigerström, Anna Johansson, Patrik Scott, Clay W Albert, Jeffrey S |
| description | We describe the development of a novel fragment screening methodology employing a plate-based optical biosensor system that can operate in a 384-well format. The method is based on the “inhibition in solution assay” (ISA) approach using an immobilized target definition compound (TDC) that has been specifically designed for this purpose by making use of available structural information. We demonstrate that this method is robust and is sufficiently sensitive to detect fragment hits as weak as KD 500 μM when confirmed in a conventional surface plasmon resonance approach. The application of the plate-based screen, the identification of fragment inhibitors of PDE10A, and their structural characterization are all discussed in a forthcoming paper. |
| doi_str_mv | 10.1021/jm301665y |
| format | Article |
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The application of the plate-based screen, the identification of fragment inhibitors of PDE10A, and their structural characterization are all discussed in a forthcoming paper.</description><subject>Biosensing Techniques</subject><subject>Drug Design</subject><subject>Drug Evaluation, Preclinical - methods</subject><subject>Phosphodiesterase Inhibitors - isolation & purification</subject><subject>Phosphoric Diester Hydrolases - drug effects</subject><subject>Surface Plasmon Resonance</subject><issn>0022-2623</issn><issn>1520-4804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkMtOwzAQRS0EgvJY8APIGyRYBPxOvKQ8KxUVCVhHTjJpXSVxsFOk8vUYCqxYzeKeOZq5CB1TckEJo5fLlhOqlFxvoRGVjCQiI2IbjQhhLGGK8T20H8KSEMIp47toj3FJtNZ0hD5u4B0a17fQDdjV2OCnxgyQjE2ACs_6wZamwWPrAnTBeXznzfybfS49QGe7OX6EYeEq17j5Gg8OT6oY23qNnxYu9DGxEAbw0YcpucKTbmELOzgfDtFObZoARz_zAL3e3b5cPyTT2f3k-mqaGE7lkFScU5EWUpQikyAJT2VaZGnJKlCQVjKrAQwIxcEomdYFU4oYTTKltdCs0vwAnW28vXdvq3hM3tpQQtOYDtwq5JSLuKgzwSN6vkFL70LwUOe9t63x65yS_Kvq_K_qyJ78aFdFC9Uf-dttBE43gClDvnQr38Uv_xF9AmNohfk</recordid><startdate>20130425</startdate><enddate>20130425</enddate><creator>Geschwindner, Stefan</creator><creator>Dekker, Niek</creator><creator>Horsefield, Rob</creator><creator>Tigerström, Anna</creator><creator>Johansson, Patrik</creator><creator>Scott, Clay W</creator><creator>Albert, Jeffrey S</creator><general>American Chemical Society</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20130425</creationdate><title>Development of a Plate-Based Optical Biosensor Fragment Screening Methodology to Identify Phosphodiesterase 10A Inhibitors</title><author>Geschwindner, Stefan ; Dekker, Niek ; Horsefield, Rob ; Tigerström, Anna ; Johansson, Patrik ; Scott, Clay W ; Albert, Jeffrey S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a315t-d33147b54c485e503757b87c2de6e7d58feeae463ea657fb2660a908699492d93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Biosensing Techniques</topic><topic>Drug Design</topic><topic>Drug Evaluation, Preclinical - methods</topic><topic>Phosphodiesterase Inhibitors - isolation & purification</topic><topic>Phosphoric Diester Hydrolases - drug effects</topic><topic>Surface Plasmon Resonance</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Geschwindner, Stefan</creatorcontrib><creatorcontrib>Dekker, Niek</creatorcontrib><creatorcontrib>Horsefield, Rob</creatorcontrib><creatorcontrib>Tigerström, Anna</creatorcontrib><creatorcontrib>Johansson, Patrik</creatorcontrib><creatorcontrib>Scott, Clay W</creatorcontrib><creatorcontrib>Albert, Jeffrey S</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Geschwindner, Stefan</au><au>Dekker, Niek</au><au>Horsefield, Rob</au><au>Tigerström, Anna</au><au>Johansson, Patrik</au><au>Scott, Clay W</au><au>Albert, Jeffrey S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Development of a Plate-Based Optical Biosensor Fragment Screening Methodology to Identify Phosphodiesterase 10A Inhibitors</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J. 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| ispartof | Journal of medicinal chemistry, 2013-04, Vol.56 (8), p.3228-3234 |
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| language | eng |
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| source | MEDLINE; American Chemical Society Journals |
| subjects | Biosensing Techniques Drug Design Drug Evaluation, Preclinical - methods Phosphodiesterase Inhibitors - isolation & purification Phosphoric Diester Hydrolases - drug effects Surface Plasmon Resonance |
| title | Development of a Plate-Based Optical Biosensor Fragment Screening Methodology to Identify Phosphodiesterase 10A Inhibitors |
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