RU-SKI 43 是一种有效的选择性刺猬酰基转移酶 (Hhat) 抑制剂,IC50为 850 nM。RU-SKI 43 通过独立于平滑化的非规范信号传导降低 Gli-1 激活,并抑制 Akt 和 mTOR 通路活性。RU-SKI 43 具有抗癌活性。
生物活性 | RU-SKI 43 is a potent and selectiveHedgehogacyltransferase(Hhat)inhibitor with anIC50of 850 nM. RU-SKI 43 reduces Gli-1 activation through Smoothened-independent non-canonical signaling and decreasesAktandmTORpathway activity. RU-SKI 43 has anti-cancer activity[1]. |
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体外研究 (In Vitro) | RU-SKI 43 (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 (10 or 20 μM; 5 hours) causes dose-dependent inhibition of Shh palmitoylation following only 5 hours[1]. RU-SKI 43 (10 μM; for 72 hours) causes a 40% decrease in Gli-1 levels in AsPC-1 cells[2]. RU-SKI 43 (10μM; 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 behaves as an uncompetitive inhibitor (Ki=7.4 μM) with respect to Shh, and as a noncompetitive inhibitor (Ki=6.9 μM) with respect to125I-iodo-palmitoylCoA[1].
Cell Proliferation Assay[2] Cell Line: | AsPC-1 and Panc-1 pancreatic cancer cells | Concentration: | 10 μM | Incubation Time: | For 6 days (drugs were replenished every 48 hours) | Result: | Strongly decreased cell proliferation (83% in AsPC-1 cells). |
Western Blot Analysis[1] Cell Line: | COS-1 cells expressing HA-Hhat and Shh | Concentration: | 10 or 20 μM | Incubation Time: | 5 hours | Result: | Caused dose-dependent inhibition of Shh palmitoylation following only 5 hours. |
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体内研究 (In Vivo) | RU-SKI 43 has a t1/2of 17 min in mouse plasma after IV administration[1].
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运输条件 | Room temperature in continental US; may vary elsewhere. |
储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |