| 名稱 | SBI-0640756 |
| 描述 | SBI-0640756 (SBI-756) (SBI-756) is a first-in-class inhibitor that targets eIF4G1 and disrupts the eIF4F complex. |
| 細(xì)胞實(shí)驗(yàn) | Cells were rinsed with PBS and lysed as previously described. Protein concentration was determined using Coomassie Plus Protein Assay Reagent. Equal amounts of cell lysate proteins (50 μg) were separated on SDS-PAGE and transferred to polyvinylidene difluoride membranes. Membranes were blocked (5% BSA/TBST, 1 h) and incubated with primary antibodies (1 h at room temperate or overnight at 4°C), with shaking. Following three TBST washes, membranes were incubated for 1 h at room temperature secondary antibodies (1:10,000). Detection and quantifications were made using Odyssey Infrared Imaging System, or by exposing them to X-ray film. Antibodies against p-AKT, p-PRAS40, p-IKK, p-IκB, p-TSC, p-mTOR, p-p70S6K, p-RPS6, p-4E-BP1, pSGK3, AKT, PRAS40, IKK, IκB, mTOR, p70S6K, RPS6, 4E-BP1, GSK3, eIF4G1, and eIF4E were purchased from Cell Signaling Technology. Antibodies against β-actin and α-tubulin were obtained from Santa Cruz Biotechnology. Secondary antibodies were goat anti-rabbit Alexa-680 F(ab')2 and goat anti-mouse IRDye 800 F(ab')2. All antibodies were used according to the suppliers' recommendations. |
| 體外活性 | SBI-0640756有效地以劑量依賴的方式使eIF4G1與eIF4E解離，伴隨著4E-BP1:eIF4E結(jié)合的同時(shí)增加，反映了eIF4F復(fù)合體形成受損。SBI-0640756還抑制了AKT/mTORC1信號(hào)傳導(dǎo)，并且mTORC1的抑制通過(guò)激活4E-BPs破壞eIF4F復(fù)合體。盡管torin1在WT中誘導(dǎo)eIF4G1與eIF4E的解離，但在4E-BP DKO MEFs中并沒(méi)有此效果，SBI-0640756在WT和4E-BP DKO MEFs中均降低了eIF4G1:eIF4E的關(guān)聯(lián)。同樣，SBI-0640756而非torin1降低了E1A/RAS轉(zhuǎn)化的4E-BP DKO MEFs的增殖。 |
| 體內(nèi)活性 | 在Ink4a 基因失活并誘導(dǎo)NRasQ61E后11周開(kāi)始僅施用SBI-0640756（大約在腫瘤出現(xiàn)前10-14天），與對(duì)照組未經(jīng)治療的動(dòng)物相比，能夠延遲腫瘤發(fā)生時(shí)間（從20-26周開(kāi)始）并且將腫瘤發(fā)生率降低了50%。對(duì)于已經(jīng)形成的腫瘤，僅使用BRAFi治療或BRAFi加SBI-0640756的組合治療都能顯著抑制腫瘤的生長(zhǎng)。 |
| 存儲(chǔ)條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Shipping with blue ice/Shipping at ambient temperature. |
| 溶解度 | 10% DMSO+40% PEG300+5% Tween 80+45% Saline : 10 mg/mL (24.7 mM), Solution.
10% DMSO+90% Saline : < 10 mg/mL (24.7 mM), Lower concentrations may be soluble, but exact solubility limit is unknown.
H2O : Insoluble
DMSO : 235 mg/mL (580.5 mM), Sonication is recommended.
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| 關(guān)鍵字 | SBI756 | SBI-0640756 | SBI0640756 | SBI 756 | Inhibitor | inhibit | Eukaryotic Initiation Factor (eIF) | eIF-4G | Autophagy |
| 相關(guān)產(chǎn)品 | Guanidine hydrochloride | Naringin | Aceglutamide | Alginic acid | Hemin | Hydroxychloroquine | Sildenafil citrate | Stavudine | Tamoxifen | Adenosine | Paeonol | Sodium 4-phenylbutyrate |
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