LY-2584702-tosylate-salt - Ribosomal S6 Kinase (RSK) 抑制劑 - 生命科學試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemELY-2584702 tosylate saltCat. No.: HY-12493ACAS No.: 1082949-68-5分式: CHFNOS分量: 617.62作靶點: Ribosomal S6 Kinase (RSK)作通路: MAPK/ERK Pathway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 : 10.25

2、mg/mL (16.60 mM; Need ultrasonic and warming)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 1 mg/mL (1.62 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 1 mg/mL (1.62 mM); Suspended solution; Need ultrasonic3. 請依序添加每種溶劑： 10% DMSO 90% corn oil1/3 Master of Small M

3、olecules 您邊的抑制劑師www.MedChemESolubility: 1 mg/mL (1.62 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 LY-2584702 tosylate salt種 ATP 競爭性的選擇性 p70S6K 抑制劑，IC50 為 4 nM。LY-2584702 抑制 S6K1的 IC50 為 2 nM。IC50 & Target S6K1 p70S6K2 nM (IC50) 4 nM (IC50)體外研究 LY-2584702 (LY2584702) inhibits phosphorylation of the S6

4、ribosomal protein (pS6) in HCT116 colon cancercells with an IC50 of 0.1-0.24 M 1. In S6K1 enzyme assay, the IC50 of LY-2584702 (LY2584702) is 2 nM.For pS6 inhibition in cells, the IC50=100 nM. LY-2584702 has some activity against the S6K-related kinasesMSK2 and RSK at high concentrations (enzyme ass

5、ay IC50=58-176 nM). LY-2584702 inhibits S6K activity inEOMA cells, as determined by the phosphorylation of its downstream effector S6, in a dose-dependentmanner 2. Proliferation of A549 is significantly inhibited by LY-2584702 (LY2584702) treating over 24 h at0.1 M (P 3.體內(nèi)研究 LY-2584702 demonstrates

6、significant single-agent efficacy in both U87MG glioblastoma and HCT116 coloncarcinoma xenograft models at two dose levels of 2.5 mg/kg twice daily (BID) and 12.5 mg/kg BID. LY-2584702 demonstrates statistically significant tumour growth reduction at TMED50 (threshold minimumeffective dose 50%) (2.3

7、 mg/kg) and TMED90 (10 mg/kg) in the HCT116 colon carcinoma xenograft model1. To examine the role of S6K in vivo, EOMA cells expressing shAkt3 are implanted in nu/nu mice, thentreated for 14 days with LY-2584702 or Rapamycin. Analysis of tumors removed after 14 days shows thatLY-2584702 inhibits S6

8、phosphorylation almost as effectively as Rapamycin. Loss of Akt3 increases tumorgrowth as compared with pLKO. LY-2584702 treatment alone does not significantly affect the growth ofpLKO tumors. However, LY-2584702 significantly reduces the growth of tumors with shAkt3 2.PROTOCOLCell Assay 3 LY-258470

9、2 is fully dissolved in 20 mL 10% DMSO and reserved at -80C. When conducted the experimentsin vitro, LY-2584702 is further diluted in 0.5% Tween 80, 5% propylene glycol and 30% PEG400 to reachdifferent DMSO concentrations of 0.1 M, 0.2 M, 0.6 M, and 1.0 M. Cell Counting Kit-8 (CCK-8) is usedto measu

10、re the cells proliferation in vitro. Cell lines A549 and SK-MES-1 treated by LY-2584702 for 24 h withdifferent concentrations are seeded in 96-well plates at a density of 5103 per well, with six repeats. DMSOtreated, or in other words, the concentration of LY-2584702 of 0 is used as negative control

11、. Cellsabsorbance at 450 nm is detected every 24 h after seeding to measure the proliferative activities 3.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 2Administration 2 LY-2584702 is prepared in 0.25% Tween-80 and 0.05% antifoam, and adm

12、inistered orally to mice (12.5mg/kg twice daily). EOMA cells (0.3106) are injected subcutaneously in 6- to 8-week-old nu/nu female mice2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE(2 sites/mouse, 4-5 mice/group). Tumor size is measured daily. For drug treatment, when tumors reach 0.01cm3 in size

13、, the animals are treated with vehicle control or LY-2584702 (12.5 mg/kg twice daily, oral dosing).Tumor size is measured every 3 to 4 days 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻 Harvard Medical School LINCS LIBRARYSee more custom

14、er validations on HYPERLINK / www.MedChemEREFERENCES1. Tolcher A, et al. A phase I trial of LY2584702 tosylate, a p70 S6 kinase inhibitor, in patients with advanced solid tumors. Eur J Cancer.2014 Mar;50(5):867-75.2. Phung TL, et al. Akt1 and akt3 exert opposing roles in the regulation of vascular tumor growth. Cancer Res. 2015 Jan 1;75(1):40-50.3. Chen B, et al. Hyperphosphorylation of RPS6KB1, rather than overexpression, predicts worse prognosis in non-small cell lung cancerpatients. PLoS One. 2017 Au