BIX02189 _MEK 抑制剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEBIX02189Cat. No.: HY-12056CAS No.: 1265916-41-3分式: CHNO分量: 440.54作靶点: MEK; ERK作通路: MAPK/ERK Pathway; Stem Cell/Wnt储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 49.4 mg/mL (112.14 mM)* mea

2、ns soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.2699 mL 11.3497 mL 22.6994 mL5 mM 0.4540 mL 2.2699 mL 4.5399 mL10 mM 0.2270 mL 1.1350 mL 2.2699 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。体内实验请根据您的实验动物和给药式选择适当的溶解案，配制前请先配制澄清的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体内实验的作液，建

3、议您现现配，当天使；澄清的储备液可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.67 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (5.67 mM); Clear solution3. 请依序添加每种溶剂： 10% DMSO 90% corn oil1/3 Maste

4、r of Small Molecules 您边的抑制剂师www.MedChemESolubility: 2.5 mg/mL (5.67 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 BIX02189种有效的选择性 MEK5 抑制剂，IC50 为 1.5 nM。BIX02189 也抑制 ERK5 活性，IC50 为 59nM。IC50 & Target MEK5 ERK5 CSF1R (FMS) LCK1.5 nM (IC50) 59 nM (IC50) 46 nM (IC50) 250 nM (IC50)JAK3 TGFR1 RPS6KA6 (RSK4)

5、RPS6KA3 (RSK2)440 nM (IC50) 580 nM (IC50) 990 nM (IC50) 2.1 M (IC50)FGFR1 KIT ABL1 MAPK14 (p38 alpha)1 M (IC50) 1.1 M (IC50) 2.4 M (IC50) 3.7 M (IC50)SRC7.6 M (IC50)体外研究 BIX02189 blocks phosphorylation of ERK5, without affecting phosphorylation of ERK1/2 in sorbitol-stimulatedHeLa cells. BIX02189 in

6、hibits ERK5 phosphorylation in a dose dependent manner 1. Fluvastatin reducesadvanced glycation endproduct (AGE)-induced vascular smooth muscle cells (VSMCs) proliferation. Toconfirm this effect, VSMCs are treated with AGEs in the presence or absence of Fluvastatin and then subjectto MTT assay. AGEs

7、 are found to dose-dependently induce cell proliferation, and this is significantlysuppressed by Fluvastatin. In addition to MTT assay, the similar results are got with cell counting. Thissuppressive effect of Fluvastatin is prevented when VSMCs are pretreated with BIX02189. Whether ERK5activation c

8、an reduce proliferation is also examined by using Ad-CA-MEK5 encoding a constitutively activemutant form of MEK5 (an upstream kinase of ERK5). AGE-induced proliferation determined by both MTTassay and cell counting is significantly diminished in the presence of Ad-CA-MEK5, and Nrf2 depletionusing si

9、RNA restored AGE-induced proliferation 2.体内研究 Mice are treated with either 10 mg/kg of BIX02189 (in 25% DMSO) or vehicle control (same volume of 25%DMSO) by intraperitoneal injection. The nuclear localization of Nrf2 is inhibited in aortic endothelial cells frommice treated with BIX02189 3.PROTOCOLC

10、ell Assay 2 AGE-induced proliferation is quantified using the MTT assay. Briefly, VSMCs are cultured on 24-well platesand when 80% confluent, medium is replaced with serum free DMEM. Cells are then pretreated withBIX02189 (2 M) and stimulated with Fluvastatin (5 M) for 24 h. MTT reagents are added f

11、or 4 h at 37C theremoved by washing with PBS, and eluted with DMSO. Proliferation is measured using a microplate readerat 570 nm 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEAnimal Mice 3Administrati

12、on 3 C57BL/6-specific pathogen-free mice are used. To determine the role of ERK5 on laminar flow-dependentNrf2 nuclear translocation in vivo, 6-week-old male C57BL/6 mice are intraperitoneally treated with BIX02189(10 mg/kg of body weight in 25% DMSO) or vehicle control. Following euthanization, vas

13、cular perfusion isperformed with saline for 5 min followed by fixation with 4% paraformaldehyde for 5 min. Isolated aorta isincubated with 0.1% PBS with Tween, and then fat is removed. 5% goat serum is used for blocking andantibody diluents. Aortic endothelial cells are stained with anti-vascular en

14、dothelial-cadherin antibody andTopro3 for endothelial cell junction and nuclear, respectively. Cellular localization of Nrf2 is determined byimmunofluorescence staining with anti-Nrf2 antibody under the Confocal microscope 3.MCE has not independently confirmed the accuracy of these methods. They are

15、 for reference only.户使本产品发表的科研献 Stem Cell Reports. 2018 Oct 9;11(4):929-943. Harvard Medical School LINCS LIBRARYSee more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Tatake RJ, et al. Identification of pharmacological inhibitors of the MEK5/ERK5 pathway. Biochem Biophys Res Commun.

16、2008 Dec5;377(1):120-5.2. Hwang AR, et al. Fluvastatin inhibits AGE-induced cell proliferation and migration via an ERK5-dependent Nrf2 pathway in vascularsmooth muscle cells. PLoS One. 2017 May 22;12(5):e0178278.3. Kim M, et al. Laminar flow activation of ERK5 protein in vascular endothelium leads to atheroprotective effect via NF-E2-related factor 2(Nrf2) activation