AEE788
作者：齊岳
發(fā)布時(shí)間：2023-09-06
09:00:48
點(diǎn)擊數(shù)：
產(chǎn)品名稱：AEE788
產(chǎn)品描述：
| 產(chǎn)品描述 | AEE788 has been used in trials studying the treatment of Cancer, Glioblastoma Multiforme, and Brain and Central Nervous System Tumors. |
| 靶點(diǎn)活性 | Flt1:59 nM, HER2/ErbB2:6 nM, c-Fms:60 nM, c-Abl:52 nM, EGFR:2 nM |
| 體外活性 | AEE788（50 mg/kg）抑制盲腸和腹膜腫瘤的生長(zhǎng)（> 50％）,并將植入裸鼠盲腸的HT29細(xì)胞的淋巴結(jié)轉(zhuǎn)移發(fā)生率降低至70％,對(duì)體重?zé)o影響.50 mg/kg AEE788作用于NeuT/ErbB2 GeMag模型誘導(dǎo)腫瘤消退達(dá)57%.AEE788有效抑制A431腫瘤中的EGF誘導(dǎo)的EGFR磷酸化和GeMag腫瘤中的erbB2磷酸化.AEE788在NCI-H596或DU145異種移植模型中產(chǎn)生對(duì)腫瘤生長(zhǎng)的劑量依賴性抑制,僅有輕微的體重變化.AEE788作用于K562腫瘤細(xì)胞,可以促進(jìn)LBH589調(diào)節(jié)的活性氧簇的產(chǎn)生,可以增強(qiáng)凋亡. AEE788劑量依賴性地抑制由VEGF誘導(dǎo)的血管生成并且不抑制bFGF誘導(dǎo)的血管生成.AEE788作用于HT29盲腸癌,明顯降低pEGFR和pVEGFR 的表達(dá)水平,但是不改變EGF,VEGF,EGFR或VEGFR的表達(dá)水平.和CPT-11聯(lián)用,AEE788明顯抑制淋巴癌轉(zhuǎn)移 AEE788抑制Daoy,DaoyPt和DaoyHER2移植瘤的生長(zhǎng),抑制分別達(dá)51%,45%和72%. |
| 體內(nèi)活性 | 0.2-1.0 μM AEE788抑制HT29細(xì)胞中EGFR和Akt的磷酸化。AEE788抑制人皮膚SCC細(xì)胞系（Colo16,HaCaT,SRB1和SRB12細(xì)胞）中EGFR,VEGFR2,Akt和MAPK的磷酸化,導(dǎo)致生長(zhǎng)抑制和誘導(dǎo)細(xì)胞凋亡。 AEE788有效抑制A431細(xì)胞中的EGFR磷酸化,IC5??0為11 nM。 AEE788還抑制CHO細(xì)胞中KDR的磷酸化和BT-474細(xì)胞中的erbB2的磷酸化,而對(duì)A31細(xì)胞中的PDGF-誘導(dǎo)的磷酸化沒有任何影響。AEE788作用于髓母細(xì)胞瘤細(xì)胞系,抑制細(xì)胞增殖,抑制EGF和神經(jīng)調(diào)節(jié)蛋白誘導(dǎo)的HER1,HER2和HER3激活。AEE788抑制NCI-H596,MK,BT-474和SK-BR-3細(xì)胞增殖,IC50分別為78,56,49和381 nM。AEE788也抑制EGF和VEGF促進(jìn)的人臍靜脈內(nèi)皮細(xì)胞增殖,IC50分別為43和155 nM。 |
| 激酶實(shí)驗(yàn) | Protein Kinase Assays: The in vitro kinase assays are performed in 96-well plates (30 μL) at ambient temperature for 15–45 min using the recombinant glutathione S-transferase-fused kinase domains (4-100 ng, depending on specific activity). [γ33P]ATP is used as phosphate donor and polyGluTyr-(4:1) peptide as acceptor. With the exception of protein kinase C-α, cyclin-dependent kinase 1/cycB and protein kinase A are protamine sulfate (200 μg/mL), histone H1 (100 μg/mL), and the heptapeptide Leu-Arg-Arg-Ala-Ser-Leu-Gly (known as Kemptide Bachem) respectively and are used as peptide substrates. Assays are optimized for each kinase using the following ATP concentrations: 1.0 μM (c-Kit, c-Met, c-Fms, c-Raf-1, and RET), 2.0 μM (EGFR, erbB2, ErbB3, and ErbB4), 5.0 μM (c-abl), 8.0 μM (Flt-1, Flt-3, Flt-4, Flk, KDR, FGFR-1, and Tek), 10.0 μM (PDGFR-β, protein kinase C-α, and cyclin-dependent kinase 1), and 20.0 μM (c-Src and protein kinase A). The reaction is terminated by the addition of 20 μL 125 mM EDTA. Thirty μL (c-abl, c-Src, insulin-like growth factor-1R, RET-Men2A, and RET-Men2B) or 40 μL (all other kinases) of the reaction mixture is transferred onto Immobilon-polyvinylidene difluoride membrane, presoaked with 0.5% H3PO4 and mounted on a vacuum manifold. Vacuum is then applied and each well rinsed with 200 μL 0.5% H3PO4. Membranes are removed and washed four times with 1.0% H3PO4 and once with ethanol. Dried membranes are counted after mounting in a Packard TopCount 96-well frame and with the addition of 10 μL/well of Microscint. IC50 values (±SE) are calculated by linear regression analysis of the percentage inhibition and are averages of at least three determinations. |
| 細(xì)胞實(shí)驗(yàn) | Methylene Blue Cell Proliferation Assay.Cells are seeded at 1.5 × 103 cells/well into 96-well microtiter plates and incubated overnight at 37 °C, 5% v/v CO2 and 80% relative humidity. AEE788 dilutions are added on day 1, with the highest concentration being 10 μM. After incubation of the cell plates for an additional 4 (T24) or 6 (BT-474, SK-BR-3, and NCI-H596) days, cells are fixed with 3.3% v/v glutaraldehyde, washed with water, and stained with 0.05% w/v methylene blue. After washing, the dye is eluted with 3% HCl and the absorbance measured at 665 nm with a SpectraMax 340 spectrophotometer. IC50 values are determined by mathematical curve-fitting and are defined as the drug concentration leading to 50% inhibition of net cell mass increase compared with untreated control cultures. (Only for Reference) |
| 別名 | NVP-AEE 788 |
| 分子量 | 440.58 |
| 分子式 | C27H32N6 |
| CAS No. | 497839-62-0 |
存儲(chǔ)
Powder: -20°C for 3 years | In solvent: -80°C for 2 years
溶解度
Ethanol: <1 mg/mL
DMSO: 82 mg/mL (186.1 mM)
( < 1 mg/mL refers to the product slightly soluble or insoluble )
聯(lián)系我們：
郵箱：2519696869@qq.com
QQ: 2519696869
電話：18066853083
微信：18066853083
公司介紹：
西安齊岳生物科技有限公司是集化學(xué)科研和定制與一體的高科技化學(xué)公司。業(yè)務(wù)范圍包括化學(xué)試劑和產(chǎn)品的研發(fā)、生產(chǎn)、銷售等。涉及產(chǎn)品為通用試劑的分銷、非通用試劑的定制與研發(fā)，涵蓋生物科技、化學(xué)品、中間體和化工材料等領(lǐng)域。
主營(yíng)產(chǎn)品：COF、MOF單體系列：三蝶烯衍生物、金剛烷衍生物、四苯甲烷衍生物、peg、上轉(zhuǎn)換、石墨烯、光電材料、點(diǎn)擊化學(xué)、凝集素、載玻片、蛋白質(zhì)交聯(lián)劑、脂質(zhì)體、蛋白、多肽、氨基酸、糖化學(xué)等。
