MTMSA-Trp

MTMSA-Trp is a synthetic analogue of mithramycin (MTM) designed with improved pharmacokinetic properties and enhanced in vivo efficacy for the treatment of Ewing sarcoma. It functions by binding to the minor groove of DNA and interacting with the EWS-FLI1 fusion oncoprotein, which is the primary driver of Ewing sarcoma. MTMSA-Trp selectively inhibits EWS-FLI1-dependent transcription and disrupts the function of oncogenic nuclear condensates. Mechanistically, it traps the EWS-FLI1 transcriptional complex, evicts the transcription factor ETV6 from the nucleus, and leads to the downregulation of CDK7 and the degradation of RNA polymerase II (RPB1). The compound was developed through a collaboration involving St. Jude Children's Research Hospital and the University of Kentucky.

Other names

mithramycin analogueMTM analogue