NSL-AB-51

NSL-AB-51 is a polyisoprenylated cysteinyl amide inhibitor (PCAI) designed to mimic the polybasic C-terminal hypervariable (HVR) region of KRAS and related proteins. Developed by researchers at Florida A&M University, it acts by binding to calmodulin, a chaperone protein essential for the trafficking and functional localization of KRAS to the plasma membrane. By disrupting these polyisoprenylation-dependent interactions, NSL-AB-51 abrogates RAS signaling, leading to decreased cell viability, inhibition of 3D spheroid invasion, and induction of apoptosis in KRAS-driven cancers such as pancreatic and breast cancer. Transcriptomic analysis indicates that NSL-AB-51 modulates genes involved in apoptosis (e.g., BBC3) and angiogenesis (e.g., ANGPTL4, EDN1).