RU-SKI 43

RU-SKI 43 is a small molecule inhibitor of Hedgehog acyltransferase (Hhat), an enzyme responsible for the palmitoylation of Hedgehog proteins, including Sonic Hedgehog (Shh). This post-translational modification is essential for the secretion and signaling activity of Shh, which is frequently overexpressed and drives tumor progression in pancreatic adenocarcinoma. Developed by researchers at Memorial Sloan-Kettering Cancer Center, RU-SKI 43 was identified via high-throughput screening and has shown the ability to inhibit Shh palmitoylation with an IC50 of approximately 0.895 µM. In preclinical studies, the compound demonstrated significant reduction in pancreatic cancer cell proliferation and tumor growth in xenograft models by disrupting both autocrine and paracrine Shh signaling pathways.