Identification of an inhibitor of the EWS-FLI1 oncogenic transcription factor by high-throughput screening.

ABSTRACT:

Background

Chromosomal translocations generating oncogenic transcription factors are the hallmark of a variety of tumors, including many sarcomas. Ewing sarcoma family of tumors (ESFTs) are characterized by the t(11;22)(q24;q12) translocation that generates the Ewing sarcoma breakpoint region 1 and Friend leukemia virus integration 1 (EWS-FLI1) fusion transcription factor responsible for the highly malignant phenotype of this tumor. Although continued expression of EWS-FLI1 is believed to be critical for ESFT cell survival, a clinically effective small-molecule inhibitor remains elusive likely because EWS-FLI1 is a transcription factor and therefore widely felt to be "undruggable."

Methods

We developed a high-throughput screen to evaluate more than 50 000 compounds for inhib

SUBMITTER: Grohar PJ 

PROVIDER: S-EPMC3119649 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature