MRT-2359 (MRT2359) is a potent, selective and orally bioavailable GSPT1-directed molecular glue degrader with DC50 of 5 nM in CAL51 cell line (Dmax=100%).
MRT-2359 potently inhibits cell viability in CAL51 cancer cell line with EC50 of 150 nM.
MRT-2359 induces the degradation of GSPT1, the associated downregulation of N-MYC and the modulation of its transcriptional output leading to preferential anti-proliferative activity in L-MYC and N-MYC driven cancer cells.
MRT-2359 administered orally demonstrates preferential anti-tumor activity in xenograft and PDX NSCLC models with high L-MYC and/or N-MYC mRNA expression levels.
MRT-2359 promotes complex formation between CRBN and GSPT1 and potently induces GSPT1 degradation in a CRBN- and degron-dependent manner.
MRT-2359 degrades GSPT1 in a large panel of cancer lines revealed profound and preferential antiproliferative activity in Myc-driven cell lines, such as high N-Myc expressing non-small cell lung cancer (NSCLC) lines and high L-Myc expressing small cell lung cancer (SCLC) lines.