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Molecules 2009, 14(9), 3589-3599; doi:10.3390/molecules14093589
Article

Development of a High-Throughput Assay for Screening of γ-Secretase Inhibitor with Endogenous Human, Mouse or Drosophila γ-Secretase

1
, 1
 and 1,2,*
1 Laboratory of Receptor-based Bio-medicine, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China 2 State Key Laboratory of Drug Research, The National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
* Author to whom correspondence should be addressed.
Received: 30 July 2009 / Revised: 22 August 2009 / Accepted: 31 August 2009 / Published: 14 September 2009
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Abstract

Selective lowering of amyloid-β levels with small-molecule γ-secretase inhibitors is a promising therapeutic approach for Alzheimer’s disease. In this work, we developed a high throughput assay for screening of γ-secretase inhibitors with endogenous γ-secretase and a fluorogenic substrate. The IC50 values of known γ-secretase inhibitors generated with this method were comparable with reported values obtained by other methods. The assay was optimized and applied to a small-scale screening of 1,280 compounds. The discovery of several new inhibitors warrants further investigation. This assay was also proven to be easily adopted to test compounds for drosophila and mouse γ-secretase, which could be very useful to assess compounds activity against γ-secretase from different species before the in vivo test in animal models.
Keywords: γ-secretase inhibitor; fluorogenic substrate; high throughput screening γ-secretase inhibitor; fluorogenic substrate; high throughput screening
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Wang, L.-F.; Zhang, R.; Xie, X. Development of a High-Throughput Assay for Screening of γ-Secretase Inhibitor with Endogenous Human, Mouse or Drosophila γ-Secretase. Molecules 2009, 14, 3589-3599.

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