NSL-YHJ-2-45

NSL-YHJ-2-45 is a small molecule polyisoprenylated cysteinyl amide inhibitor (PCAI) being developed by researchers at Florida A&M University for the treatment of RAS-driven cancers, specifically pancreatic cancer. PCAIs represent a novel class of anticancer agents designed to target polyisoprenylation-dependent processes of hyperactive mutant or overexpressed G-proteins, such as KRAS, RHOA, and CDC42. In preclinical evaluations using the PANC-1 pancreatic cancer cell line, NSL-YHJ-2-45 demonstrated significant potency with an EC50 value of 3.6 µM. The compound's mechanism of action involves the modulation of key oncogenic signaling pathways, including the MAPK and PI3K/AKT pathways. Treatment with PCAIs has been shown to alter the phosphorylation states of downstream kinases like BRAF, MEK, ERK, and AKT, while simultaneously reducing the protein levels of monomeric G-proteins, thereby inhibiting the growth and viability of pancreatic cancer cells.