- 抑制劑
- 化合物庫
- 抗體
- 生物試劑
- qPCR
- 2x SYBR Green qPCR Master Mix
- 2x SYBR Green qPCR Master Mix(Low ROX)
- 2x SYBR Green qPCR Master Mix(High ROX)
- 蛋白實(shí)驗(yàn)
- Protein A/G免疫沉淀磁珠
- Anti-DYKDDDDK Tag免疫磁珠
- Anti-DYKDDDDK Tag親和凝膠
- Anti-Myc免疫磁珠
- Anti-HA免疫磁珠
- 磁力架
- Poly DYKDDDDK Tag多肽
- 細(xì)胞核與細(xì)胞漿蛋白抽提試劑盒
- 免疫磁珠
- 蛋白酶抑制劑Cocktail
- 蛋白酶抑制劑Cocktail(DMSO儲液)
- 磷酸酶抑制劑Cocktail
- 細(xì)胞實(shí)驗(yàn)
- Cell Counting Kit-8 (CCK-8)
- 新產(chǎn)品
- 聯(lián)系我們
Selisistat (EX 527)
別名: SEN0014196
Selisistat (EX 527, SEN0014196) 是一種有效的，選擇性SIRT1抑制劑，無細(xì)胞試驗(yàn)中IC50為38 nM，比作用于SIRT2和SIRT3選擇性高200倍以上。Phase 2。
Selisistat (EX 527) Chemical Structure
CAS: 49843-98-3
產(chǎn)品質(zhì)控
批次：
純度：
99.78%
99.78
Selisistat (EX 527)相關(guān)產(chǎn)品
| 相關(guān)靶點(diǎn) | SIRT1 SIRT2 SIRT3 SIRT6 SIRT5 | 點(diǎn)擊展開 |
|---|---|---|
| 相關(guān)產(chǎn)品 | SRT1720 HCl Sirtinol 3-TYP AGK2 OSS_128167 SRT2104 (GSK2245840) SirReal2 Thiomyristoyl Salvianolic acid B SRT2183 UBCS039 Salermide SRT3025 HCl AK 7 Inauhzin NRD167 CAY10602 | 點(diǎn)擊展開 |
| 相關(guān)化合物庫 | 激酶抑制劑庫 FDA藥物庫 天然產(chǎn)物庫 已知活性藥物庫-I 高選擇性抑制劑庫 | 點(diǎn)擊展開 |
相關(guān)信號通路圖
細(xì)胞實(shí)驗(yàn)數(shù)據(jù)示例
| 細(xì)胞系 | 實(shí)驗(yàn)類型 | 給藥濃度 | 孵育時間 | 活性描述 | 文獻(xiàn)信息(PMID) |
|---|---|---|---|---|---|
| HUVECs | Apoptosis Assay | 10?μM | 24 h | bolishes the protective effect of resveratrol in cell viability | 23358928 |
| RMECs | Apoptosis Assay | 10?μM | 24?h | attenuates the anti-apoptotic effect of Des-G | 24486147 |
| Platelets | Apoptosis Assay | 10/50 μM | 10 min | increases ROS level in a dose-dependent manner | 25829495 |
| K562 | Function Assay | 0.1-1 μM | 2 h | stimulates Nrf2-dependent gene transcription | 21196497 |
| INS-1E | Function Assay | 1 μm | 24 h | prevents resveratrol-induced up-regulation of?Glut2, glucokinase,Pdx-1, and?Tfam | 21163946 |
| MCF-7? | Growth Inhibition Assay | 0-100 μM | 24/48/72 h | represses cell proliferation at the concentration ≥100 μM | 20371709 |
| NCI-H460? | Function Assay | 1 μm | 6 h | produces a concentration-dependent increase in the amount of acetylated p53 | 16354677 |
| HCT116 | Function assay | 10 uM | 8 hrs | Inhibition of SIRT1 in human HCT116 cells assessed as increase in acetylated p53 at 10 uM after 8 hrs by Western blot analysis | 22642300 |
| HeLa | Growth Inhibition Assay | 48 h | IC50=8.9?±?1.9 μM | 24998427 | |
| HEK 293 | Growth Inhibition Assay | 48 h | IC50=69.0?±?0.7 μM | 24998427 | |
| HeLa | Growth Inhibition Assay | 24 h | IC50=37.9?±?1.8 μM | 24998427 | |
| HEK 293 | Growth Inhibition Assay | 24 h | IC50=97.7 ± 8.1 μM | 24998427 | |
| Namalwa cells | Function assay | 3 hrs | Inhibition of SIRT1-mediated endogenous p53 deacetylase activity in human Namalwa cells assessed as concentration required to enhance p53 deacetylation to twice the basal level after 3 hrs by ELISA, INH = 0.6 μM. | 25971769 | |
| Hs683 | Cell cycle assay | 24 to 48 hrs | Cell cycle arrest in human Hs683 cells assessed as accumulation at G1 phase at IC50 after 24 to 48 hrs by propidium iodide staining-based flow cytometry | 28475330 | |
| NCI-H460 | Function assay | 6 hrs | Inhibition of SIRT-2 in human NCI-H460 cells assessed as inhibition of p53 deacetylation after 6 hrs by immunoprecipitation/immunoblotting analysis, IC50 = 1 μM. | ChEMBL | |
| 293T | Function assay | Inhibition of human recombinant GST-tagged SIRT1 expressed in 293T cells by Fluor de Lys fluorescence assay, IC50 = 0.038 μM. | 21306906 | ||
| Escherichia coli cells | Function assay | Inhibition of human recombinant SIRT1 expressed in Escherichia coli cells using acetylated Lys side chain amino acids 379-382 (Arg-His-Lys-Lys(Ac)) p53 conjugated with aminomethylcoumarin as substrate by fluorescence assay, IC50 = 0.16 μM. | 22931526 | ||
| BL21 (DE3) | Function assay | Inhibition of full length human SIRT1 expressed in Escherichia coli BL21 (DE3) cells using fluorogenic 7-amino-4-methylcoumarin (AMC)-labeled peptide by fluorescence assay, IC50 = 0.21 μM. | 25275824 | ||
| BL21 (DE3) | Function assay | Inhibition of full length human SIRT2 expressed in Escherichia coli BL21 (DE3) cells using fluorogenic 7-amino-4-methylcoumarin (AMC)-labeled peptide by fluorescence assay, IC50 = 1.94 μM. | 25275824 | ||
| Escherichia coli cells | Function assay | Inhibition of human recombinant SIRT2 expressed in Escherichia coli cells using acetylated Lys side chain amino acids 379-382 (Arg-His-Lys-Lys(Ac)) p53 conjugated with aminomethylcoumarin as substrate by fluorescence assay, IC50 = 48.5 μM. | 22931526 | ||
| A673 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells | 29435139 | ||
| SK-N-MC | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells | 29435139 | ||
| 點(diǎn)擊查看更多細(xì)胞系數(shù)據(jù) | |||||
生物活性
| 產(chǎn)品描述 | Selisistat (EX 527, SEN0014196) 是一種有效的，選擇性SIRT1抑制劑，無細(xì)胞試驗(yàn)中IC50為38 nM，比作用于SIRT2和SIRT3選擇性高200倍以上。Phase 2。 | ||
|---|---|---|---|
| 特性 | 與其他SIRT1抑制劑相比，EX 527有效性，特定性，和穩(wěn)定性更高，且毒性更低。 | ||
| 靶點(diǎn) |
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| 體外研究(In Vitro) | ||||||
| 體外研究活性 | EX 527有效抑制SIRT1去乙酰化酶活性，IC50為38 nM, 這種作用存在濃度依賴性，而抑制SIRT2和SIRT3時，效果低很多，IC50分別為19.6 μM和48.7 μM。EX 527 濃度高達(dá)100 μM時也不抑制SIRT4-7和I/II類 HDAC活性。1 μM EX-527 單獨(dú)作用于NCI-H460 細(xì)胞，不能檢測p53在lysine 382位點(diǎn)的乙酰化作用。EX-527作用于受遺傳毒性試劑和H2O2影響的NCI-H460細(xì)胞，人類乳腺上皮細(xì)胞,U-2 OS 和MCF-7 細(xì)胞，顯著提高乙酰化p53的量。但是EX 527在p53控制的基因表達(dá), 細(xì)胞存活,或細(xì)胞增殖方面沒有檢測效果。[1] EX 527 在0.1% 血清而不是10%血清中處理7天，作用于HCT116細(xì)胞，顯著提高細(xì)胞數(shù)，提高達(dá)90%，說明在無細(xì)胞因子的情況下，SirT1是細(xì)胞增殖的顯著調(diào)節(jié)器。[2] EX 527 作用于INS-1E細(xì)胞,廢除白藜蘆醇對葡萄糖的反應(yīng)的影響，且抑制白藜蘆醇誘導(dǎo)的Glut2, 葡萄糖激酶，Pdx-1,和Tfam的上調(diào), 因?yàn)镋X 527和白藜蘆醇作用于SIRT1脫乙酰基酶活性的作用是相反的。[3] |
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|---|---|---|---|---|---|---|
| 激酶實(shí)驗(yàn) | GST-SIRT1脫乙酰基酶實(shí)驗(yàn) | |||||
| 在pDEST27 Gateway載體中使用FuGENE-6使293T細(xì)胞短暫轉(zhuǎn)染GST標(biāo)記的人SIRT1。 48小時后,用50 mM Tris, pH 8.0, 120 mM NaCl, 1 mM EDTA,和 0.5% Nonidet P-40溶解細(xì)胞，加入完整Mini蛋白酶抑制劑片。使用谷胱甘肽-瓊脂糖凝膠珠從溶解物中純化GST-SIRT1，然后在以上buffer 中進(jìn)行沖洗。在EX 527 (48 pM 到100 μM)存在時，使用30 ng GST-SIRT1進(jìn)行脫乙酰反應(yīng)。使用Fluor de Lys 試劑盒 ，使用包含p53的379到 382 殘基，且在lysine 382位點(diǎn)乙酰化的熒光肽，測定脫乙酰作用。使乙酰化賴氨酸殘基與一部分aminomethylcoumarin進(jìn)行耦合。SIRT1使肽段脫乙酰化,隨后加入蛋白水解顯影劑，釋放熒光aminomethylcoumarin。酶和170 μM NAD+及100 μM p53熒光肽在37oC下溫育45分鐘，隨后在顯影劑中溫育15分鐘。分別在460 nm處測定熒光值，用相對熒光單位表示酶活性。 | ||||||
| 細(xì)胞實(shí)驗(yàn) | 細(xì)胞系 | NCI-H460, MCF-7, U-2 OS和 HMEC | ||||
| 濃度 | 溶于 DMSO, 終濃度為1 μM | |||||
| 孵育時間 | 48 或72小時 | |||||
| 方法 | 測定細(xì)胞活力, 用 EX 527處理細(xì)胞48小時。通過細(xì)胞Titer-Glo熒光實(shí)驗(yàn)測定細(xì)胞活力,測定全部 ATP水平，作為細(xì)胞數(shù)的一個指數(shù)。在Luminoskan Ascent讀數(shù)儀上測定熒光值。測定增殖實(shí)驗(yàn)中,在培養(yǎng)基中加入EX 527，然后立即加入0.5 μCi/mL [14C]胸甘。在Microbeta液體閃爍計數(shù)器上測量，在48小時(測定HMEC)或72小時(測定NCI-H460, MCF-7, 和U-2 OS細(xì)胞)測定實(shí)驗(yàn)板。在Cytostar-T組織培養(yǎng)板上通過接近閃爍體而測定滲透到細(xì)胞的胸甘。 |
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| 實(shí)驗(yàn)圖片 | 檢測方法 | 檢測指標(biāo) | 實(shí)驗(yàn)圖片 | PMID | ||
| Western blot |
GRP78 / FASL / Bcl-2 / LC3
Ac-H3K9 / Fibronectin / Collagen 1 / α-SMA
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