LLC0150

LLC0150 is a potent proteolysis-targeting chimera (PROTAC) designed to induce the degradation of Nuclear Receptor Binding SET Domain Protein 2 (NSD2), also known as WHSC1 or MMSET. NSD2 is an H3K36 di-methyltransferase that serves as a critical coactivator for the androgen receptor (AR) in prostate cancer, particularly in the context of neo-enhanceosome complexes that drive metastatic gene programs. By degrading NSD2, LLC0150 disrupts AR-mediated transcription and exhibits selective cytotoxicity in AR/FOXA1-positive prostate cancer cells. Additionally, LLC0150 has shown preclinical activity against NSD2-mutant acute lymphocytic leukemia and multiple myeloma, where NSD2 is often overexpressed or mutated. The compound was developed through a collaboration between the University of Michigan and the Shanghai Institute of Organic Chemistry.