Hhat Inhibitor, RU-SKI 43

A cell-permeable dihydrothienopyridinyl-ethanone compound that acts as an effective inhibitor against MBOAT (membrane-bound O-acyltranferase) family member Hhat/hedgehog acyltransferase-catalyzed ShhN palmitoylation in cell-free assays (by 70% at 12.5 µM) in a palmitoyl CoA-noncompetitive (K_i = 6,9 µM; [ShhN] = 38 µM) and ShhN-uncompetitive (K_i = 7.4 µM; [palmitoyCoA] = 30 µM) manner. Effectively prevents Shh- & Hhat-transfected COS-1 cells from activating hedgehog signaling in co-cultured C3H10T1/2 cells (~80% inhibition of AP production in 30 min with10 µM inhibitor) by inhibiting COS-1 intracellular ShhN palmitoylation (by 52% and 80%, respectively, with 10 or 20 µM drug treatment and serum withdrawal 1 h before 4 h [¹²⁵I]-palmitate incubation). RU-SKI 43 is shown not to interfere with cellular palmitoylation of H-ras & fyn, myristoylation of c-Src & Wnt3a, Shh autoprosessing, or the protein level and localization of Shh & Hhat. Exhibits short plasma half-life in mice (t_1/2 = 17 min; i.v.).

A cell-permeable dihydrothienopyridinyl-ethanone compound that acts as an effective inhibitor against MBOAT family member Hhat/hedgehog acyltransferase-catalyzed ShhN palmitoylation in a palmitoyl CoA-noncompetitive (K_i = 6,9 µM; [ShhN] = 38 µM) and ShhN-uncompetitive (K_i = 7.4 µM; [palmitoyCoA] = 30 µM) manner. Effectively prevents Shh- & Hhat-transfected COS-1 cells from activating hedgehog signaling in co-cultured C3H10T1/2 cells (~80% inhibition with10 µM inhibitor) by inhibiting COS-1 intracellular ShhN palmitoylation (by 52% and 80%, respectively, with 10 or 20 µM drug treatment) without affecting cellular palmitoylation of H-ras & fyn, myristoylation of c-Src & Wnt3a, Shh autoprosessing, or the protein level and localization of Shh & Hhat. Exhibits short plasma half-life in mice (t_1/2 = 17 min; i.v.).

Cell permeable: yes

Primary Target
Hhat

Reversible: yes

Packaged under inert gas

Toxicity: Standard Handling (A)

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

Petrova, E., et al. 2013. Nat. Chem. Biol.9, 247.

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