Development of a Plate-Based Optical Biosensor Fragment Screening Methodology to Identify Phosphodiesterase 10A Inhibitors

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• 作者：Stefan Geschwindner ; Niek Dekker ; Rob Horsefield ; Anna Tigerstr枚m ; Patrik Johansson ; Clay W. Scott ; Jeffrey S. Albert
• 刊名：Journal of Medicinal Chemistry
• 出版年：2013
• 出版时间：April 25, 2013
• 年：2013
• 卷：56
• 期：8
• 页码：3228-3234
• 全文大小：288K
• 年卷期：v.56,no.8(April 25, 2013)
• ISSN：1520-4804

文摘

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 鈥渋nhibition in solution assay鈥?(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 渭M 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.