| 名稱 | Onatasertib |
| 描述 | Onatasertib (CC223) is an orally available mTOR inhibitor with potential antitumor activity. Onatasertib inhibits the activity of mTOR, which may result in the induction of tumor cell apoptosis and a decrease in tumor cell proliferation. Onatasertib is a potent mTOR kinase inhibitor (IC50: 16 nM), with >150-fold sensitivity than the related lipid kinase PI3Kα (IC50: 4 μM). |
| 細(xì)胞實驗 | Compound is spotted via an acoustic dispenser (EDC ATS-100) into an empty 384-well plate. Cells are diluted to desired densities and added directly to the compound-spotted plates. Cells are allowed to grow for 72 hours. Viability is assessed via Cell Titer-Glo. All data are normalized and represented as a percentage of the DMSO-treated cells. Results are then expressed as GI50 and/or IC50 values.(Only for Reference) |
| 激酶實驗 | Kinase assays mTOR.: Reagents are prepared as follows:"Simple Tor buffer": 10 mM Tris pH 7.4, 100 mM NaCl, 0.1% Tween-20, 1 mM DTT. Recombinant mTOR is diluted in this buffer to an assay concentration of 0.200ug/mL. ATP/Substrate solution: 0.075 mM ATP, 12.5 mM MnCl2, 50 mM Hepes, pH 7.4, 50 mM β-GOP, 250 nM Microcystin LR, 0.25 mM EDTA, 5 mM DTT, and 3.5 μg/mL GST-p70S6. Dilution Curve: A 10-point, 1:3 dilution of compounds are prepared in neat DMSO at 50 times the final assay concentration. Detection reagent mix: 50 mM HEPES, pH 7.4 0.01% Triton X-100, 0.01% BSA, 0.1 mM EDTA, 12.7 ug/mL Cy5-anti-GST antibody, 9 ng/ml anti-phospho p70S6 antibody (Thr389), 627ng/mL anti-mouse IgG labeled with Lance Eu. To 20 uL of the Simple Tor buffer is added 0.5 uL of the compound Dilution Curve in DMSO. The final concentration range for compound is 30 to 0.0015 μM. To initiate the reaction, 5 μL of the ATP/substrate solution is added to the above. The reaction is allowed to run for 60 minutes. The assay is stopped by adding 5 μL of 60 mM EDTA. Ten (10) μL of detection reagent mix is then added, and the mixture is allowed to sit at least 2 hours before reading on a Perkin Elmer Envision microplate reader set to detect Europium-based TR-FRET. |
| 體外活性 | 在PC-3腫瘤移植的小鼠中,CC-223 (25 mg/kg,p.o.)抑制了mTORC1和mTORC2的活性.CC-223 (25 mg/kg, p.o.)還抑制了許多腫瘤模型的腫瘤生長,包括前列腺癌,神經(jīng)膠質(zhì)瘤,乳腺癌,肺癌以及結(jié)腸癌模型（47%-95%）. |
| 體內(nèi)活性 | 在許多的細(xì)胞系中,CC-223對mTORC1 (S6RP and 4EBP1)和mTORC2 [AKT(S473)]標(biāo)記物均有抑制作用,其IC50為pAKT（S473,11-150 nM）,pS6RP（27-184 nM）,p4EBP1（120-1050 nM）。CC-223還對許多癌細(xì)胞系的生長有抑制作用并誘導(dǎo)它們凋亡。 |
| 存儲條件 | Store at low temperature,Keep away from direct sunlight
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Shipping with blue ice/Shipping at ambient temperature. |
| 溶解度 | DMSO : 125 mg/mL (314.49 mM), Sonication is recommended.
10% DMSO+40% PEG300+5% Tween 80+45% Saline : 2 mg/mL (5.03 mM), Sonication is recommended.
Ethanol : 73 mg/mL (183.66 mM), Sonication is recommended.
H2O : < 1 mg/mL (insoluble or slightly soluble)
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| 關(guān)鍵字 | PI3K-α | Onatasertib | mTOR | Mammalian target of Rapamycin | Inhibitor | inhibit | FLT4 | DNA-PK | DNAPK | c-Fms | cFms | ATG-008 | ATG008 | ATG 008 | Apoptosis |
| 相關(guān)產(chǎn)品 | Formamide | Urea | Sodium Molybdate | Dimethyl phthalate | Aceglutamide | Alginic acid | Cysteamine hydrochloride | Metronidazole | Sildenafil citrate | Citric Acid Triammonium | Stavudine | Tamoxifen |
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