Hedgehog acyltransferase (Hhat) is an N-palmitoyltransferase that acylates Sonic hedgehog (Shh), which is critical for signaling through Shh. RU-SKI 43 is an inhibitor of Hhat (IC50 = 0.85 ?M).1 It blocks palmitoylation of Shh without affecting palmitoylation of H-Ras or Fyn, myristoylation of c-Src, or acylation of Wnt3a.1 RU-SKI 43 is cell-permeable and inhibits both autocrine and paracrine Shh-induced activation of Gli-mediated transcription.1 In pancreatic cancer cells, RU-SKI 43 reduces both Gli1 activation and proliferation.2
1.Petrova, E., Rios-Esteves, J., Ourfelli, O., et al.Inhibitors of Hedgehog acyltransferase block Sonic Hedgehog signalingNat. Chem. Biol.9(4)247-249(2013) 2.Petrova, E., Matevossian, A., and Resh, M.D.Hedgehog acyltransferase as a target in pancreatic ductal adenocarcinomaOncogene34263-268(2015)