Establishment and Application of High-throughput Screening Model for SHP Inhibitors
GAO Wei1, SHAO Wei2, SU Gang2, LI Jia3, XIE Xiaodong2
1. Department of General Thoracic Surgery, Lanzhou General Hospital of Lanzhou Military Command, Lanzhou 730050, China;
2. Key Lab of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Science of Lanzhou University, Lanzhou 730020, China;
3. National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Science, Shanghai 201203, China
Abstract：The aims of this study is to set up a high throughput screening model for SHP2 inhibitors and screen the potential inhibitors. By the E. coil expression system GST-SHP2 fusion protein is cloned and over expressed. High-purity SHP2 protein is purified though GSTSepharose column. After establishing the high through screening system with the colorimetric assay of SHP2, a library of 48000 pure compounds is screened using the 384 micro- plate. Among them 75 compounds have inhibitory effects over 50%. Ultimately, three inhibitors are identified as SHP2 inhibitors with high activity. The high throughput screening is a highly sensitive, inexpensive, and operationally simple assay method in identifying SHP2 inhibitors.
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2014, Vol. 32 
