产品说明书

OSU-03012

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Chemical Structure| 742112-33-0 同义名 : AR-12;PDK1 inhibitor AR-12
CAS号 : 742112-33-0
货号 : A152748
分子式 : C26H19F3N4O
纯度 : 99%+
分子量 : 460.45
MDL号 : MFCD12912272
存储条件：

粉末 Keep in dark place,Inert atmosphere,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(228.04 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

0.5% methylcellulose+0.2% Tween 80+water 30 mg/mL suspension

生物活性
靶点

  • PDK1

    PDK-1, IC50:5 μM
描述 3'-Phosphoinositide-dependent protein kinase 1 (PDK-1) phosphorylates and activates members of the AGC protein kinase family and plays an important role in the regulation of cell survival, differentiation, and proliferation[3]. OSU-03012 is a PDK-1 inhibitor with an IC50 of 5 μM. OSU-03012 induces apoptotic death in PC-3 cells in 1% FBS-containing medium in a dose-dependent manner, as demonstrated by DNA fragmentation and PARP cleavage. It is effective in suppressing PC-3 cell proliferation at sub-μM, consistent with that noted in 1% serum. OSU-03012 was able to completely suppress cell growth in a diverse range of tumor cell lines at the 3-5 μM therapeutic range, as compared with the concentration of at least 50 μM required for celecoxib[4]. OSU-03012 inhibited cell growth of Huh7, Hep3B, and HepG2 cells with IC50 below 1 mumol/L[5]. Daily oral treatment of BALB/c nude mice with OSU-03012 suppressed the growth of Huh7 tumor xenografts. Electron microscopic observation indicated that OSU-03012 induced autophagy in vivo[5]. OSU-03012 remarkably decreases EGFR protein expression in the tumors by ~48% compared with expression levels found in the tumors taken from mice that receive the vehicle control. OSU-03012 also prevents Y-box binding protein-1 (YB-1) from binding to the EGFR promoter at the 1b and 2a sites[6].
作用机制 The guanidino group of OSU-03012 resembled the partial structure of the purine ring of ATP, which allowed the formation of hydrogen bonds with Ser160 and Ala162 as depicted by the docking model.
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
mouse RAW264.7 cells Function assay 8 h Antimicrobial activity against Salmonella enterica serovar Typhimurium ATCC 14028 infected in mouse RAW264.7 cells assessed as inhibition of intracellular bacterial growth after 8 hrs, IC50=0.2 μM 19805568
mouse RAW264.7 cells Cytotoxic assay 24 h Cytotoxicity against mouse RAW264.7 cells assessed as cell viability after 24 hrs by MTT assay, IC50=10 μM 19805568
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.17mL

0.43mL

0.22mL

10.86mL

2.17mL

1.09mL

21.72mL

4.34mL

2.17mL
参考文献

[1]Yacoub A, Park MA, et al. OSU-03012 promotes caspase-independent but PERK-, cathepsin B-, BID-, and AIF-dependent killing of transformed cells. Mol Pharmacol. 2006 Aug;70(2):589-603.

[2]Zhu J, Huang JW, et al. From the cyclooxygenase-2 inhibitor celecoxib to a novel class of 3-phosphoinositide-dependent protein kinase-1 inhibitors. Cancer Res. 2004 Jun 15;64(12):4309-18.

[3]Lim MA, Kikani CK, Wick MJ, Dong LQ. Nuclear translocation of 3'-phosphoinositide-dependent protein kinase 1 (PDK-1): a potential regulatory mechanism for PDK-1 function. Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14006-11. doi: 10.1073/pnas.2335486100. Epub 2003 Nov 17. PMID: 14623982; PMCID: PMC283536.

[4]Zhu J, Huang JW, Tseng PH, Yang YT, Fowble J, Shiau CW, Shaw YJ, Kulp SK, Chen CS. From the cyclooxygenase-2 inhibitor celecoxib to a novel class of 3-phosphoinositide-dependent protein kinase-1 inhibitors. Cancer Res. 2004 Jun 15;64(12):4309-18. doi: 10.1158/0008-5472.CAN-03-4063. Erratum in: Cancer Res. 2019 Apr 1;79(7):1716. PMID: 15205346.

[5]Gao M, Yeh PY, Lu YS, Hsu CH, Chen KF, Lee WC, Feng WC, Chen CS, Kuo ML, Cheng AL. OSU-03012, a novel celecoxib derivative, induces reactive oxygen species-related autophagy in hepatocellular carcinoma. Cancer Res. 2008 Nov 15;68(22):9348-57. doi: 10.1158/0008-5472.CAN-08-1642. PMID: 19010909.

[6]To K, Zhao Y, Jiang H, Hu K, Wang M, Wu J, Lee C, Yokom DW, Stratford AL, Klinge U, Mertens PR, Chen CS, Bally M, Yapp D, Dunn SE. The phosphoinositide-dependent kinase-1 inhibitor 2-amino-N-[4-[5-(2-phenanthrenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]phenyl]-acetamide (OSU-03012) prevents Y-box binding protein-1 from inducing epidermal growth factor receptor. Mol Pharmacol. 2007 Sep;72(3):641-52. doi: 10.1124/mol.107.036111. Epub 2007 Jun 26. Erratum in: Mol Pharmacol. 2014 Mar;85(3):531-2. PMID: 17595327.