| 名稱 | Ixazomib |
| 描述 | Ixazomib (MLN2238) , a second generation, boron-containing peptide proteasome inhibitor (PI), inhibits the chymotrypsin-like proteolytic (β5) site of the 20S proteasome (IC50/Ki: 3.4/0.93 nM, in cell-free assays), also inhibits the caspase-like (β1) and trypsin-like (β2) proteolytic sites (IC50: 31/3500 nM). |
| 細(xì)胞實驗 | Calu-6 cells are cultured in MEM containing 10% FBS and 1% penicillin/streptomycin and plated 1 day before the start of the experiment at 1 × 104 cells per well in a 384-well plate. For IC50 determinations, cells are treated with varying concentrations of Bortezomib or MLN2238 in DMSO (0.5% final, v/v) for 1 hour at 37 °C. For reversibility experiments, cells are treated with either 1 μM Bortezomib or MLN2238 for 30 minutes at 37 °C and then washed thrice in medium to remove the Bortezomib or MLN2238. Cells are incubated for an additional 4 hours at 37 °C, after which the medium is removed and replaced with fresh medium. (Only for Reference) |
| 激酶實驗 | Kinase assay : Calu-6 cells are cultured in MEM containing 10% fetal bovine serum and 1% penicillin/streptomycin and plated 1 day before the start of the experiment at 1 × 104 cells per well in a 384-well plate. Proteasome activity is assessed by monitoring hydrolysis of the chymotrypsin-like substrate Suc-LLVY-aminoluciferin in the presence of luciferase using the Proteasome-Glo assay reagents according to the manufacturer's instructions. Luminescence is measured using a LEADseeker instrument. |
| 體外活性 | MLN2238對CWR22移植瘤具有抗癌活性.在WSU-DLCL2移植瘤模型中,MLN2238的腫瘤藥效反應(yīng)比bortezomib更強(qiáng). 此外,在OCI-Ly10和PHTX22L模型中,MLN2238比 bortezomib具有更高的藥效和抗癌活性.作用于移植瘤時,MLN2238的藥效反應(yīng)比bortezomib更較強(qiáng),且其最大值更高,對腫瘤蛋白酶的抑制效果更持久. |
| 體內(nèi)活性 | MLN2238是MLN9708的生物活性代謝物。MLN2238和Bortezomib均為時間依賴性的蛋白酶體可逆抑制劑,但與Bortezomib(110分鐘)相比,MLN2238（18分鐘）作用于蛋白酶體的分離半衰期要快6倍。MLN2238的腫瘤藥效 要高于Bortezomib。MLN2238是氮端加帽的二肽亮氨酸硼酸,對20S 蛋白酶體中糜蛋白酶類的水解位點有抑制作用（IC50/Ki：3.4/0.93 nM）。更高濃度時,MLN2238對20S蛋白酶體的caspase類水解位點（IC50：31 nM）和胰蛋白酶類水解位點（IC50：3.5 μM）也有抑制作用。MLN2238抑制Calu-6細(xì)胞（IC50：9.7 nM）。 |
| 存儲條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| 溶解度 | 10% DMSO+40% PEG300+5% Tween 80+45% Saline : 2 mg/mL (5.54 mM), Sonication is recommended.
DMSO : 55 mg/mL (152.34 mM), Sonication is recommended.
Ethanol : 9 mg/mL (24.93 mM), Sonication is recommended.
H2O : < 1 mg/mL (insoluble or slightly soluble)
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| 關(guān)鍵字 | Proteasome | MLN-2238 | MLN 2238 | Ixazomib | Inhibitor | inhibit | caspase-like (β1) | Autophagy | 20S proteasome |
| 相關(guān)產(chǎn)品 | Guanidine hydrochloride | Naringin | Enzalutamide | Aceglutamide | Alginic acid | Cysteamine hydrochloride | Hemin | Hydroxychloroquine | Sildenafil citrate | Stavudine | Tamoxifen | Paeonol |
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