ecteinascidin derivative 2

Ecteinascidin derivative 2 is a novel synthetic small molecule analog of lurbinectedin, currently in preclinical development for the treatment of advanced cancers, particularly skin cutaneous melanoma (SKCM). Developed by researchers at the IGBMC (University of Strasbourg), this compound is designed to combat transcriptional addiction—the dependence of cancer cells on high transcriptional activity of specific oncogenes. Mechanistically, it functions as a pan-inhibitor of super-enhancer (SE)-driven oncogenic transcription. It achieves this by directly binding to and inhibiting the promoters of genes that encode ubiquitous transcription factors and coactivators enriched at SE sites. Preclinical data presented at AACR 2025 indicates that this derivative, along with its parent compound lurbinectedin, exhibits potent anti-tumor activity in melanoma models, including those resistant to standard therapies, by suppressing oncogenic expression and prolonging survival in mouse xenografts.