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1782573-67-4

中文名稱(chēng) RU-SKI 43 HCL;HHAT INHIBITOR
英文名稱(chēng) 2-(2-methylbutylamino)-1-[4-[(3-methylphenoxy)methyl]-6,7-dihydro-4H-thieno[3,2-c]pyridin-5-yl]ethanone:hydrochloride
CAS 1782573-67-4
分子式 C22H31ClN2O2S
分子量 423.01
MOL 文件 1782573-67-4.mol
更新日期 2024/11/15 18:20:34
1782573-67-4 結(jié)構(gòu)式 1782573-67-4 結(jié)構(gòu)式

基本信息

中文別名
RU-SKI 43(鹽酸鹽)
英文別名
RU-SKI 43 HCL
HHAT INHIBITOR
2-(2-methylbutylamino)-1-[4-[(3-methylphenoxy)methyl]-6,7-dihydro-4H-thieno[3,2-c]pyridin-5-yl]ethanone:hydrochloride

物理化學(xué)性質(zhì)

儲(chǔ)存條件-20°C儲(chǔ)存
溶解度DMF: 30 mg/ml; DMSO: 30 mg/ml; Ethanol: 30 mg/ml; Ethanol:PBS(pH 7.2) (1:1): 0.5 mg/ml
形態(tài)結(jié)晶固體
顏色White to off-white

常見(jiàn)問(wèn)題列表

生物活性
RU-SKI 43 hydrochloride 是一種有效的選擇性刺猬?;D(zhuǎn)移酶 (Hhat) 抑制劑,IC50 為 850 nM。RU-SKI 43 hydrochloride 通過(guò)獨(dú)立于平滑化的非規(guī)范信號(hào)傳導(dǎo)降低 Gli-1 激活,并抑制 Akt 和 mTOR 通路活性。RU-SKI 43 hydrochloride 具有抗癌活性。
靶點(diǎn)

IC50: 850 nM (Hhat)

體外研究

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.
RU-SKI 43 hydrochloride (10 or 20 μM; 5 hours) causes dose-dependent inhibition of Shh palmitoylation following only 5 hours.
RU-SKI 43 hydrochloride (10 μM; for 72 hours) causes a 40% decrease in Gli-1 levels in AsPC-1 cells.
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.
RU-SKI 43 hydrochloride behaves as an uncompetitive inhibitor (K i =7.4 μM) with respect to Shh, and as a noncompetitive inhibitor (K i =6.9 μM) with respect to 125 I-iodo-palmitoylCoA.

Cell Proliferation Assay

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

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.
體內(nèi)研究

RU-SKI 43 hydrochloride has a t 1/2 of 17 min in mouse plasma after IV administration.

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