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RU-SKI 43 is the first potent and specific small molecule inhibitor of Hedgehog acyltransferase (Hhat), and directly inhibits palmitoylation of the Shh ligand. It was discovered by a high-throughput screen using a peptide-based assay to monitor Hhat-mediated Shh palmitoylation (IC₅₀ ~0.85 µM). In vitro using purified Hhat and ShhN to analyze the kinetics of compound’s inhibition of ShhN palmitoylation, RU-SKI 43 behaved as an uncompetitive inhibitor (Ki = 7.4 μM) with respect to Shh and as a noncompetitive inhibitor (Ki = 6.9 μM) with respect to [¹²⁵I]iodo-palmitoyl CoA. In cells, RU-SKI 43 specifically blocks Shh palmitoylation and inhibits autocrine and paracrine Shh signaling. Hhat inhibitor could offer a new treatment modality for cancers characterized by Shh overexpression and extremely poor prognoses.

How to Use:

• In vitro: RU-SKI 43 was used at 10-20 µM final concentration in vitro and in cellular assays.
• In vivo: n/a

Reference:

1. 1. Petrova E, et al. Inhibitors of Hedgehog acyltransferase block Sonic Hedgehog signaling. (2013) Nat Chem Biol. 9(4):247-9.
2. 2. Petrova E, et al. Hedgehog acyltransferase as a target in pancreatic ductal adenocarcinoma. (2014) Oncogene. In press.

Products are for research use only. Not for human use.