| Description | RU-SKI 43 is a potent and selective hedgehog acyltransferase (Hhat) inhibitor with an IC50 of 850 nM.RU-SKI 43 has anticancer activity and is a potential compound for the treatment of lung adenocarcinomas.RU-SKI 43 reduces Gli-1 activation through smoothing-independent non-canonical signalling and inhibits Akt and mTOR pathway activity. |
| In vitro | RU-SKI 43（10或20 μM；5小时；AsPC-1和Panc-1胰腺癌细胞）在仅5小时内导致Shh棕榈酰化级别的剂量依赖性抑制。[1] RU-SKI 43作为对Shh的非竞争性抑制剂，具有7.4 μM的Ki值，而对于125I-碘棕榈酰CoA，其Ki值为6.9 μM。[1] RU-SKI 43（10μM；48小时；AsPC-1和Panc-1胰腺癌细胞）导致Akt途径中四种蛋白的磷酸化减少（下降47-67％），这四种蛋白包括在Thr307和Ser473位点磷酸化的Akt、PRAS40、Bad和GSK-3β。此外，RU-SKI 43处理还减少了mTOR信号途径中成分mTOR和S6的磷酸化水平。[2] RU-SKI 43（10 μM；6天）显著抑制了AsPC-1和Panc-1细胞的增殖（AsPC-1细胞中减少83％）。[2] RU-SKI 43（10 μM；72小时；AsPC-1和Panc-1胰腺癌细胞）使AsPC-1细胞中的Gli-1水平下降40％。[2] |
| In vivo | 静脉注射后，RU-SKI 43在小鼠血浆中的半衰期为17分钟。[1] |
| Target activity | Hhat:850 nM, [125I]-iodo-palmitoylCoA:6.9 μM(Ki), Shh:7.4 μM(Ki) |
| Synonyms | RUSKI 43 |
| molecular weight | 386.55 |
| Molecular formula | C22H30N2O2S |
| CAS | 1043797-53-0 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| References | 1. Petrova E, et al. Inhibitors of Hedgehog acyltransferase block Sonic Hedgehog signaling.Nat Chem Biol. 2013 Apr;9(4):247-9. 2. Petrova E, et al. Hedgehog acyltransferase as a target in pancreatic ductal adenocarcinoma. Oncogene. 2014 Jan 27. |