YD23

YD23 is a selective **proteolysis-targeting chimera (PROTAC)** designed to induce the degradation of **SMARCA2**, a catalytic subunit of the SWI/SNF chromatin remodeling complex. Developed through structure-activity relationship studies, YD23 binds to and selectively depletes SMARCA2 protein within cells, leading to profound reprogramming of the enhancer landscape, especially in cells harboring mutations in the SMARCA4 gene. This synthetic lethal approach results in potent anti-tumor activity, particularly against SMARCA4-mutant non-small cell lung cancer (NSCLC) models, by disrupting cell proliferation programs regulated by SMARCA2. YD23 shows strong selectivity, sparing SMARCA4-wild-type cells and demonstrating preclinical efficacy in xenograft studies.