Last Updated: 04/06/07
Development of Novel High-Throughput Screening Technology for Identification of Inhibitors of Transcription Factor-DNA Binding
STB investigators worked with Dr. Charles Vinson, CCR Laboratory of Metabolism, to develop, optimize, and characterize a screen for four of the B-Zip family of transcription factors that are known to have oncogenic effects. A high-throughput screen of the NCI diversity set identified a single chemotype effective in disrupting B-Zip–DNA interactions. Further work is in progress to define the activity of this chemotype in cell-based reporters for B-Zip activity and to evaluate additional leads identified in high-throughput screening of chemical libraries. STB investigators have generalized this technology to develop a screen for inhibitors of ASPL-TFE3 chimeric transcription factor-DNA interaction. This chimeric transcription factor results from a chromosomal translocation characteristic of alveolar soft-part sarcoma. In sarcoma and in other pediatric tumors, such as alveolar rhabdomyosarcoma, the chromosomal translocation and associated chimeric transcription factor present a potentially exploitable therapeutic target.
Rishi V, Potter T, Laudeman J, Reinhart R, Silvers T, Selby M, Stevenson T, Krosky P, Stephen AG, Acharya A, Moll J, Oh WJ, Scudiero D, Shoemaker RH, Vinson C. A high-throughput fluorescence-anisotropy screen that identifies small molecule inhibitors of the DNA binding of B-ZIP transcription factors. Anal Biochem 2005;340:259–71.
