ra413s

RA413S is the S-enantiomer of a chiral benzylidenepiperidone derivative, developed as a small molecule inhibitor targeting RPN13 (ADRM1), a ubiquitin receptor within the 19S regulatory particle of the proteasome. RA413S exhibits potent cytotoxicity in cancer cell lines, notably showing greater cytotoxicity for HeLa cells and other ovarian and cervical cancer cell lines compared to its R enantiomer (RA413R). Its mechanism involves selective binding to RPN13, leading to ATP depletion, mitochondrial damage, oxidative stress, and inhibition of glutathione and NF-κB, which results in apoptosis of tumor cells. RA413S shows weaker cytotoxicity in normal human cells and represents a new class of targeted anti-cancer agents with improved specificity for RPN13[3].