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受注：045-509-1970 |
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化学情報
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Synonyms | N/A | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
| 化学式 | C26H19F3N4O |
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| 分子量 | 460.45 | CAS No. | 742112-33-0 | |
| Solubility (25°C)* | 体外 | DMSO | 92 mg/mL (199.8 mM) | |
| Ethanol | 7 mg/mL (15.2 mM) | |||
| Water | Insoluble | |||
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* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. |
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溶剤液（一定の濃度）を調合する
生物活性
| 製品説明 | OSU-03012 (AR-12) is a potent inhibitor of recombinant PDK-1(phosphoinositide-dependent kinase 1) with IC50 of 5 μM in a cell-free assay and 2-fold increase in potency over OSU-02067. |
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| in vitro | OSU-03012 induces apoptotic death in PC-3 cells with IC50 of 5 µM and reduces the activity of immunoprecipitated p70S6K. OSU-03012 completely suppress cell growth in a diverse range of tumor cell lines at concentrations of 3–5 μm, as compared with the concentration of at least 50 μm. [1] OSU-03012 promotes cell killing to a greater extent in glioma cells than in nontransformed astrocytes. OSU-03012 causes a dose-dependent induction of cell death that is not altered by p53 mutation, expression of ERBB1 VIII, or loss of phosphatase and tensin function due to a homolog deletion on chromosome 10. OSU-03012 and ionizing radiation cause an additive, caspase-independent elevation in cell killing. OSU-03012 lethality as a single agent or when combined with signaling modulators is not modified in cells lacking expression of BIM or of BAX/BAK. OSU-03012 promotes the release of cathepsin B from the lysosomal compartment and that of AIF from mitochondria. The lethality of OSU-03012 is attenuated in protein kinase R-like endoplasmic reticulum kinase-/- cells, which correlated with the reduced cleavage of BID and suppression of cathepsin B and AIF release into the cytosol. [2] OSU-03012 inhibits thyroid cancer cell (NPA, WRO, and ARO cells) proliferation, migration and induces apoptosis, which results in an increase of cells in the S phase without an increase of cells in G2. OSU-03012 is an ATP-competitive inhibitor of PAK activity and suppresses the phosphorylation of AKT in thyroid cancer cells. [3] OSU-03012 inhibits cell growth of hepatocellular carcinoma cell lines including Huh7, Hep3B and HepG2 cells with IC50 values below 1 μM. OSU-03012 does not suppress PDK1 or AKT activity or induce cellular apoptosis but induces autophagy in Huh7 cells. Moreover, accumulation of reactive oxygen species (ROS) is detected after OSU-03012 treatment. [4] A recent study shows that OSU-03012 could enhance the susceptibility of (Bcr)-Abl mutant cell lines to -induced apoptosis. [5] |
| in vivo | OSU-03012 suppresses tumor growth by 57.59% and increases cleaved LC3 in Huh7 tumor xenografts at 200 mg/kg. [4] OSU-03012 remarkably decreases expression of EGFR protein in the tumors by 48% compared with vehicle controls and also prevents YB-1 from binding to the EGFR promoter in MDA-MB-435/LCC6 xenografts. [6] OSU-03012 is well tolerated and inhibits the growth of HMS-97 schwannoma xenografts by 55% after oral administration. [7] |
プロトコル(参考用のみ)
| キナーゼアッセイ | PDK-1 Kinase Assay | |
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| 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. | ||
| 細胞アッセイ | 細胞株 | PC-3 cells |
| 濃度 | 0-10 μM | |
| 反応時間 | ~72 hours | |
| 実験の流れ | 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. |
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| 動物実験 | 動物モデル | Huh7 tumor xenografts in male BALB/c nude mice |
| 投薬量 | 100-200 mg/kg | |
| 投与方法 | Daily by gavage | |
参考
カスタマーフィードバック
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Data from [Data independently produced by J Biol Chem, 2014, 289(38), 26155-66]
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Data from [Data independently produced by PLoS One, 2013, 8, e75100]
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Data from [Anticancer Drugs, 2013, 24(7), 690-8]
Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：
| NAC1 confines virus-specific memory formation of CD4+ T cells through the ROCK1-mediated pathway [ J Med Virol, 2023, 95(7):e28957] | PubMed: 37465969 |
| Salmonella effector SopF regulates PANoptosis of intestinal epithelial cells to aggravate systemic infection [ Gut Microbes, 2023, 15(1):2180315] | PubMed: 36803521 |
| AR12 increases BAG3 expression which is essential for Tau and APP degradation via LC3-associated phagocytosis and macroautophagy [ Aging (Albany NY), 2022, 14(20):8221-8242] | PubMed: 36227739 |
| Pulmonary fibrosis distal airway epithelia are dynamically and structurally dysfunctional [ Nat Commun, 2021, 12(1):4566] | PubMed: 34315881 |
| Development of potent dual PDK1/AurA kinase inhibitors for cancer therapy: Lead-optimization, structural insights, and ADME-Tox profile [ Eur J Med Chem, 2021, 226:113895] | PubMed: 34624821 |
| Decanoic Acid Stimulates Autophagy in D. discoideum [ Cells, 2021, 10(11)2946] | PubMed: 34831171 |
| Inhibition of heat shock proteins increases autophagosome formation, and reduces the expression of APP, Tau, SOD1 G93A and TDP-43 [ Aging (Albany NY), 2021, 13(13):17097-17117] | PubMed: 34252884 |
| OSU-03012 Disrupts Akt Signaling and Prevents Endometrial Carcinoma Progression in vitro and in vivo [ Drug Des Devel Ther, 2021, 15:1797-1810] | PubMed: 33958857 |
| Metabolic Modifier Screen Reveals Secondary Targets of Protein Kinase Inhibitors Within Nucleotide Metabolism [ Cell Chem Biol, 2020, 20;27(2):197-205.e6] | PubMed: 31734178 |
| A facile and sensitive method of quantifying glutaminase binding to its inhibitor CB-839 in tissues [ J Genet Genomics, 2020, 47(7):389-395] | PubMed: 33004309 |
長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。