Ewing’s sarcoma is characterized by the formation of an oncogenic fusion protein, EWS-FLI1, which binds to RNA helicase central to disease. YK-4-279 binds to EWS-FLI1 (Kd = 9.48 μM), blocking the interaction of EWS-FLI1 and RNA helicase and driving apoptosis in Ewing’s sarcoma family tumors. Through these effects, YK-4-279 reduces the growth of Ewing’s sarcoma orthotopic xenografts. Importantly, it is effective in Ewing’s sarcoma cells, both in vitro and in vivo, that are chemotherapy-resistant. YK-4-279 also binds the ETS transcription factors ERG and ETV1 (Kd = 11.7 and 17.4, respectively), which form fusion proteins that contribute to some types of prostate cancer. (+)-YK-4-279 is a highly purified enantiomer of YK-4-279. Its properties have not been characterized.
