Development of Mithramycin Analogs for Ewing sarcoma
A promising drug target for Ewing’s sarcoma is a protein called EWS-FLI1. This is a type of protein called a transcription factor which is thought by many to be an “undruggable target.”
The focus of this study is to develop a compound called EC8042 as a bona fide inhibitor of EWS-FLI1. We will show that the drug blocks EWS-FLI1 using sophisticated sequencing technologies on a genome wide scale. In addition, we will use animal models to optimize the suppression of EWS-FLI1 in vivo. We will use Positron Emission Tomography (PET) imaging to follow EWS-FLI1 suppression in the tumors of the mice. Together, these results will provide the data to justify and guide the development and translation of this compound to the clinic as an EWS-FLI1 inhibitor.