SW43

SW43 is a small molecule sigma-2 (σ2) receptor ligand being investigated for the treatment of pancreatic cancer. The σ2 receptor was recently identified as transmembrane protein 97 (TMEM97), a protein localized in the lysosome and endoplasmic reticulum that regulates cholesterol export in coordination with NPC1. SW43 targets endo-lysosomal compartments and disrupts lysosomal cholesterol transport, causing dose-dependent sequestration of cholesterol within lysosomes. This mechanism leads to cancer cell death and has demonstrated synergistic activity when combined with the HMG-CoA reductase inhibitor simvastatin. The compound was developed by researchers at Washington University in St. Louis.