| 名稱 | Osu03012 |
| 描述 | Osu03012 (AR-12) is an orally bioavailable, small-molecule, celecoxib-derived inhibitor of phosphoinositide-dependent kinase-1 (PDK1) with potential antineoplastic activity. |
| 細(xì)胞實驗 | The effect of OSU-03012 on PC-3 cell viability is assessed by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay in six replicates. Cells are grown in 10% FBS- supplemented RPMI 1640 in 96-well, flat-bottomed plates for 24 hours. They are exposed to various concentrations of OSU-03012 (0-10 μM) dissolved in DMSO (final concentration ≤0.1%) in 1% serum-containing RPMI 1640 for different time intervals (~72 hours). Controls receive DMSO vehicle at a concentration equal to that in OSU-03012-treated cells. The medium is removed and replaced by 200 μL of 0.5 mg/mL 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide in 10% FBS-containing RPMI 1640. The cells are incubated in the CO2 incubator at 37 °C for 2 hours. Supernatants are removed from the wells, and the reduced 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide dye is solubilized in 200 μL DMSO per well. Absorbance at 570 nm is determined by using a plate reader.(Only for Reference) |
| 激酶實驗 | PDK-1 Kinase Assay: This in vitro assay is performed using a PDK-1 kinase assay kit. This cell-free assay is based on the ability of recombinant PDK-1, in the presence of DMSO vehicle or OSU-03012, to activate its downstream serum- and glucocorticoid-regulated kinase which, in turn, phosphorylates the Akt/serum- and glucocorticoid-regulated kinase-specific peptide substrate RPRAATF with [γ-32P]ATP. The 32P-phosphorylated peptide substrate is then separated from the residual [γ-32P]-ATP by using P81 phosphocellulose paper and quantitated in a scintillation counter after three washes with 0.75% phosphoric acid. |
| 體外活性 | 在MDA-MB-435 / LCC6異種移植物模型中,OSU-03012顯著降低腫瘤中EGFR蛋白的表達(dá),同時還阻止YB-1與的EGFR啟動子結(jié)合.在Huh7 移植瘤中,OSU-03012（200 mg/kg）能夠抑制腫瘤細(xì)胞生長.在HMS-97神經(jīng)鞘瘤異種移植物模型中,口服給藥OSU-03012能夠抑制細(xì)胞生長. |
| 體內(nèi)活性 | OSU-03012濃度為3-5 μM時即可完全抑制多種腫瘤細(xì)胞生長。在甲狀腺癌細(xì)胞(NPA, WRO和ARO細(xì)胞)中,OSU-03012作為ATP競爭性抑制劑,通過 抑制PAK活性和AKT磷酸化,從而抑制細(xì)胞增殖和遷移,誘導(dǎo)細(xì)胞凋亡。在肝細(xì)胞癌細(xì)胞系（Huh7, Hep3B和HepG2細(xì)胞）中,OSU-03012（IC50<1 μM）抑制細(xì)胞生長。其中,對于Huh7細(xì)胞,OSU-03012誘導(dǎo)細(xì)胞發(fā)生自噬。在神經(jīng)膠質(zhì)瘤細(xì)胞、PC-3細(xì)胞中,OSU-03012能夠促進(jìn)細(xì)胞凋亡。 |
| 存儲條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | Ethanol : < 1 mg/mL (insoluble or slightly soluble)
H2O : < 1 mg/mL (insoluble or slightly soluble)
DMSO : 70 mg/mL (152.03 mM)
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| 關(guān)鍵字 | AR12 | AR 12 | Osu03012 |
| 相關(guān)產(chǎn)品 | RS1-PDK1 inhibitor | 6-Bromo-4-methoxypyrazolo[1,5-a]pyridine-3-carbonitrile | M77976 | PHT-427 | BX795 | GSK2334470 | Rabusertib | Polyphyllin I | PS 48 | MP7 | Dehydroabiethylamine | Sodium dichloroacetate |
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