RU-SKI 43 hydrochloride

• CAT Number: R065387
• CAS Number: 1782573-67-4
• Molecular Formula: C22H31ClN2O2S
• Molecular Weight: 423.01
• Purity: ≥95%
• Synonyms: 2-(2-methylbutylamino)-1-[4-[(3-methylphenoxy)methyl]-6,7-dihydro-4H-thieno[3,2-c]pyridin-5-yl]ethanone;hydrochloride
• InChI: InChI=1S/C22H30N2O2S.ClH/c1-4-16(2)13-23-14-22(25)24-10-8-21-19(9-11-27-21)20(24)15-26-18-7-5-6-17(3)12-18;/h5-7,9,11-12,16,20,23H,4,8,10,13-15H2,1-3H3;1H
• InChIKey: JBBKLHJLHRGJSQ-UHFFFAOYSA-N
• SMILES: CCC(C)CNCC(=O)N1CCC2=C(C1COC3=CC=CC(=C3)C)C=CS2.Cl

RU-SKI 43 hydrochloride is a potent and selective Hedgehog acyltransferase (Hhat) inhibitor with an IC50 of 850 nM. RU-SKI 43 hydrochloride reduces Gli-1 activation through Smoothened-independent non-canonical signaling and decreases Akt and mTOR pathway activity. RU-SKI 43 hydrochloride has anti-cancer activity[1].
RU-SKI 43 hydrochloride (10 μM; for 6 days) strongly decreases cell proliferation (83% in AsPC-1 cells) in AsPC-1 and Panc-1 cells[2].
RU-SKI 43 hydrochloride (10 or 20 μM; 5 hours) causes dose-dependent inhibition of Shh palmitoylation following only 5 hours[1].
RU-SKI 43 hydrochloride (10 μM; for 72 hours) causes a 40% decrease in Gli-1 levels in AsPC-1 cells[2].
RU-SKI 43 hydrochloride (10 μM; 48 hours) results in decreased phosphorylation (47-67%) of four proteins in the Akt pathway, including Akt (phosphorylation at both Thr307 and Ser473), PRAS40, Bad and GSK-3β. RU-SKI 43 treatment also decreases phosphorylation of mTOR and S6, members of the mTOR signaling pathway[2].
RU-SKI 43 hydrochloride behaves 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-palmitoylCoA[1].
RU-SKI 43 hydrochloride has a t1/2 of 17 min in mouse plasma after IV administration[1].

Reference

[1]. Petrova E, et al. Inhibitors of Hedgehog acyltransferase block Sonic Hedgehog signaling.Nat Chem Biol. 2013 Apr;9(4):247-9.
 [Content Brief]

[2]. Petrova E, et al. Hedgehog acyltransferase as a target in pancreatic ductal adenocarcinoma. Oncogene. 2014 Jan 27. doi: 10.1038/onc.2013.575.
 [Content Brief]