OSU-03012 (AR-12)是一种有效的重组PDK-1抑制剂，IC50为5 μM，比OSU-02067作用效果高2倍。OSU-03012诱导PC-3细胞凋亡，IC50为5 µM，且降低免疫沉淀的p70S6K的活性。Celecoxib完全抑制肿瘤细胞生长,浓度至少需要50 μM，而OSU-03012浓度为3-5 μM时即可完全抑制多种肿瘤细胞生长。 与作用于正常的胶质细胞相比，OSU-03012作用于神经胶质瘤细胞更有效促进细胞死亡。
store at -20℃ for one year（Powder）；
in DMSO or others solvent store at 2-4℃ for two weeks, at -20℃ for six months.
DMSO ：9 mg/mL (19.5 mM)
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 required for celecoxib. 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. 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. 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. A recent study shows that OSU-03012 could enhance the susceptibility of (Bcr)-Abl mutant cell lines to imatinib-induced apoptosis.
OSU-03012 suppresses tumor growth by 57.59% and increases cleaved LC3 in Huh7 tumor xenografts at 200 mg/kg. 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. OSU-03012 is well tolerated and inhibits the growth of HMS-97 schwannoma xenografts by 55% after oral administration.
OSU-03012 suppresses GRP78/BiP expression that causes PERK-dependent increases in tumor cell killing.
Booth et al. Cancer Biol Ther. 2012 Feb 15;13(4):224-36. PMID: 22354011.
Endogenous adenosine contributes to renal sympathetic neurotransmission via postjunctional A1 receptor-mediated coincident signaling.
Jackson et al. Am J Physiol Renal Physiol. 2012 Feb;302(4):F466-76. PMID: 22114202.
The phosphoinositide-3-kinase-Akt signaling pathway is important for Staphylococcus aureus internalization by endothelial cells.
Oviedo-Boyso et al. Infect Immun. 2011 Nov;79(11):4569-77. PMID: 21844240.
OSU-03012, a novel celecoxib derivative, induces cell swelling and shortens action potential duration in mouse ventricular cells.
Yamamoto et al. Biomed Res. 2010 Dec;31(6):413-7. PMID: 21187652.
OSU-03012 enhances Ad.7-induced GBM cell killing via ER stress and autophagy and by decreasing expression of mitochondrial protective proteins.
Hamed et al. Cancer Biol Ther. 2010 Apr;9(7):526-36. PMID: 20107314.
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李晓勇, 刘涛, 李建, 刘超, 刘宇宏
中国细胞生物学学报. 2020 Jan 01 ; 1