NSL-AB-02

NSL-AB-02 is a small molecule polyisoprenylated phosphonyl ester inhibitor (PPEI) designed as a farnesyl-targeted irreversible inhibitor of polyisoprenylated methylated protein methyl esterase (PMPMEase). Developed at Florida A&M University, the compound targets the regulatory enzymes of monomeric G-proteins (such as KRAS, CDC42, RHOA, and RAC1) that require polyisoprenylation and methylation for functional activity. In preclinical models of pancreatic cancer, NSL-AB-02 has shown potent anti-proliferative activity, induction of apoptosis through caspase activation, and disruption of the MAPK and PI3K/AKT signaling pathways. Additionally, treatment leads to the reorganization of actin filaments, resulting in the loss of cancer cell shape and rounding.