OSU-03012-AR-12-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEOSU-03012Cat. No.: HY-10547CAS No.: 742112-33-0Synonyms: AR-12分式: CHFNO分量: 460.45作靶點: PDK-1; Autophagy作通路: PI3K/Akt/mTOR; Autophagy儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 100 mg/mL

2、(217.18 mM)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.43 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemESolubility: 2.5 mg/mL (5.43 mM); Suspended solution; Need ultrasonic3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSo

3、lubility: 2.5 mg/mL (5.43 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 OSU-03012種 PDK-1 抑制劑，IC50 為 5 M。IC50 & Target IC50: 5 M (PDK-1) 1體外研究 OSU-03012 inhibits PC-3 cells viability with IC50 values of 5 M. The effects of OSU-03012 on PC-3 cellproliferation in 10% FBS-supplemented medium are also examin

4、ed. OSU-03012 induces apoptotic death inPC-3 cells in 1% FBS-containing medium in a dose-dependent manner, as demonstrated by DNAfragmentation and PARP cleavage. OSU-03012 is effective in suppressing PC-3 cell proliferation at sub-M,consistent with that noted in 1% serum 1.體內(nèi)研究 All of the SCID/Rag2

5、mice develop two MDA-MB-435/LCC6/Her-2 tumors and are assigned to either thevehicle control or OSU-03012 (200 mg/kg) treatment group, which is given orally for 3 days. OSU-03012remarkably decreases EGFR protein expression in the tumors by 48% compared with expression levelsfound in the tumors taken

6、from mice that receive the vehicle control. OSU-03012 also prevents Y-box bindingprotein-1 (YB-1) from binding to the EGFR promoter at the 1b and 2a sites 2.PROTOCOLCell Assay 1 PC-3 (p53-/-) human androgen-nonresponsive prostate cancer cells are cultured in RPMI 1640supplemented with 10% fetal bovi

7、ne serum (FBS) at 37C in a humidified incubator containing 5% CO2. Theeffect of Celecoxib and its derivatives (e.g., OSU-03012) (2.5 M, 5 M, 7.5 M and 10 M) on PC-3 cellviability is assessed by using the MTT assay in six replicates. Cells are grown in 10% FBS- supplementedRPMI 1640 in 96-well, flat-

8、bottomed plates for 24 h, and are exposed to various concentrations of Celecoxibderivatives (e.g., OSU-03012) dissolved in DMSO (final concentration 0.1%) in 1% serum-containing RPMI1640 for different time intervals. Controls receive DMSO vehicle at a concentration equal to that in drug-treated cell

9、s. The medium is removed, replaced by 200 L of 0.5 mg/mL of MTT in 10% FBS-containingRPMI 1640, and cells are incubated in the CO2 incubator at 37C for 2 h. Supernatants are removed fromthe wells, and the reduced MTT dye is solubilized in 200 L/well DMSO. Absorbance at 570 nm isdetermined on a plate

10、 reader 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 2Administration 2 SCID/Rag2m mice (6-8 weeks old, female) are subcutaneously injected with 1107 MDA-MB-435/LCC6 cellsstably transfected with HER-2/neu. Each mouse is inoculated with t

11、he cells on the right and left sides of thelower back. A total of eight mice are injected, each harboring two tumors. After 6 weeks, the mice arerandomly assigned into groups (vehicle, 0.5% methyl cellulose/0.1% Tween 80, or OSU-03012 at 2002/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEmg/kg/day)

12、. Mice are dosed daily for 3 days with either the vehicle or OSU-03012 by oral gavage. On thefourth day, the study is terminated, mice are sacrificed, and the tumors are collected for chromatinimmunoprecipitation (ChIP) and protein isolations.MCE has not independently confirmed the accuracy of these

13、 methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻 Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Zhu J, et al. From the cyclooxygenase-2 inhibitor celecoxib to a novel class of 3-phosphoinositide-dependent protein kinase-1 inh

14、ibitors.Cancer Res. 2004 Jun 15;64(12):4309-18.2. To K, et al. The phosphoinositide-dependent kinase-1 inhibitor 2-amino-N-4-5-(2-phenanthrenyl)-3-(trifluoromethyl)-1H-pyrazol-1-ylphenyl-acetamide (OSU-03012) prevents Y-box binding protein-1 from inducing epidermal growth factor receptor. Mol Pharmacol. 2007Sep;72(3