| 名稱 | NVP-AEW541 |
| 描述 | NVP-AEW541 (AEW541), a potent inhibitor of IGF-1R(IC50=150 nM) and InsR(IC50=140 nM), exhibits excellent efficiency and specificity for IGF-1R in a cell-based assay. |
| 細(xì)胞實(shí)驗(yàn) | Between 3 × 103 and 6 × 103 cells/well are seeded in 96-well plates with a total media volume of 100 μL/well. Increasing concentrations of NVP-AEW541 is added 24 hours thereafter in quadruplicate. 72 hours later, cells are fixed by addition of 25 μL/well Glutaraldehyde (20%) and incubation for 10 min at RT. Cells are then washed 2× with 200 μL/well Water and 100 μL Methylene Blue (0.05%) is added. After incubation for 10 min at RT, cells are washed 3× with 200 μL/well Water. 200 μL/well HCl (3%) is added, and following incubation for 30 min at RT on a plate shaker, absorbance is measured at 650 nm.(Only for Reference) |
| 激酶實(shí)驗(yàn) | In vitro kinase assays: NVP-AEW541 is dissolved in DMSO (10 mM) and stored at -20 °C. Dilutions are freshly made in DMSO/water 1:1. The final concentration of DMSO in the enzyme assays is <0.5 %. The protein kinase assays are carried out in 96-well plates at RT and terminated by the addition of 20 μL of 125 mM EDTA. Subsequently, 30 μL (c-Abl, c-Src, IGF-1R) of the reaction mixture are transferred onto Immobilon-PVDF presoaked for 5 min with methanol, rinsed with water, then soaked for 5 min with 0.5 % H3PO4 and mounted on vacuum manifold. After spotting all samples, vacuum is connected and each well rinsed with 200 μL 0.5 % H3PO4. Membranes are removed and washed 4× on a shaker with 1.0 % H3PO4, once with ethanol. After drying, mounting in Packard TopCount 96-well frame, and adding of 10 μL/well of Microscint, membranes are counted. IC50 values are calculated by linear regression analysis of the percentage inhibition of NVP-AEW541 in duplicate, at four concentrations (usually 0.01, 0.1, 1, and 10 μM). One unit of protein kinase activity is defined as 1 nmol of 33P transferred from [γ33P]ATP to the substrate protein per minute per mg of protein at 37 °C. |
| 體外活性 | NVP-AEW541可抑制InsR、Tek、Flt1和Flt3的活性，其IC50分別為140 nM、530 nM、600 nM和420 nM，表現(xiàn)在純化激酶/重組激酶域測定中。其對細(xì)胞水平上InsR的選擇性更高，效力提高了27倍。NVP-AEW541能夠抑制IGF-I介導(dǎo)的MCF-7細(xì)胞存活、軟瓊脂生長及增殖，相應(yīng)IC50為0.162 μM、0.105 μM和1.64 μM。同時，NVP-AEW541還能降低NWT-21細(xì)胞中的磷酸化IGF-1R和磷酸化PKB水平。[1] NVP-AEW541顯示出在低血清培養(yǎng)基及含10% FBS培養(yǎng)基中對TC-71肌肉骨骼肉瘤細(xì)胞的生長抑制效果，并在肉瘤細(xì)胞系（TC-71, SK-N-MC, SaoS-2, RD/18和RH4）中抑制細(xì)胞周期進(jìn)程，誘導(dǎo)特異性G1階段阻滯。[2] NVP-AEW541能抑制人類神經(jīng)母細(xì)胞瘤細(xì)胞的生長，IC50范圍為0.4-6.8 μM。這些細(xì)胞系可檢測到次二倍體分?jǐn)?shù)增加以及S和G2-M部分的耗盡。NVP-AEW541驅(qū)動的IGF-1R抑制導(dǎo)致Akt磷酸化減少，但不影響Erk1和Erk2。[3] NVP-AEW541抑制膠質(zhì)瘤細(xì)胞生長并破壞由HIF1α穩(wěn)定化引起的自分泌回路。[4] 最近的研究顯示，NVP-AEW541抑制PC3、DU145和22Rv1前列腺癌細(xì)胞的增殖和活力，而不必然導(dǎo)致相關(guān)細(xì)胞死亡。NVP-AEW541在22Rv1和DU415細(xì)胞中降低磷酸化Akt水平，但PC3細(xì)胞除外，不影響總Akt水平，表明PTEN狀態(tài)可能決定了含必需Akt的NVP-AEW541的有效性。NVP-AEW541誘導(dǎo)的增敏作用依賴于Akt激活狀態(tài)。NVP-AEW541能增加PC3、DU145和22Rv1細(xì)胞中H2AX磷酸化（DSB的一個衡量指標(biāo)）。[5] |
| 體內(nèi)活性 | NVP-AEW541（50 mg/kg，口服）能夠抑制基礎(chǔ)及IGF-I誘導(dǎo)的受體以及PKB和MAPK的磷酸化，NWT-21腫瘤移植物中的T/C值為14%。[1] NVP-AEW541（50 mg/kg）在HTLA-230和SK-N-BE2c腫瘤移植物中均能引起腫瘤縮小，且未見全身毒性跡象。NVP-AEW541能夠在Matrigel-coated室和HTLA-230腫瘤移植物中抑制腫瘤侵襲。[3] |
| 存儲條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | DMSO : 51 mg/mL (116.03 mM), Sonication is recommended.
H2O : < 1 mg/mL (insoluble or slightly soluble)
Ethanol : < 1 mg/mL (insoluble or slightly soluble)
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| 關(guān)鍵字 | TyrosineKinases | Tyrosine Kinases | Tek | NVP-AEW-541 | NVP-AEW541 | NVPAEW541 | NVP-AEW 541 | NVP AEW541 | Insulin Receptor | Inhibitor | inhibit | IGF-1R | IGF1R | FLT3 | FLT1 | Autophagy | AEW-541 | AEW 541 |
| 相關(guān)產(chǎn)品 | Oxyresveratrol | Guanidine hydrochloride | Naringin | Valproic Acid | Taurine | Gefitinib | Aceglutamide | Hydroxychloroquine | Curcumin | Stavudine | Paeonol | Sodium 4-phenylbutyrate |
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