BIX-02565 - Ribosomal S6 Kinase (RSK) 抑制剂 - 生命科学试剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEBIX 02565Cat. No.: HY-16104CAS No.: 1311367-27-7分式: CHNO分量: 458.56作靶点: Ribosomal S6 Kinase (RSK)作通路: MAPK/ERK Pathway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 : 20.75 mg/mL (45.25 mM; N

2、eed ultrasonic and warming)Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.1807 mL 10.9037 mL 21.8074 mL5 mM 0.4361 mL 2.1807 mL 4.3615 mL10 mM 0.2181 mL 1.0904 mL 2.1807 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，建议您现现配，当

3、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: 1.67 mg/mL (3.64 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 1.67 mg/mL (3.64 mM); Clear solutionBIOLOGICAL ACTIVITY1/3 Master of Small Molecules 您边的抑制剂师www.Med

4、ChemE物活性 BIX 02565种有效的核糖体 S6 激酶 2 (RSK2) 抑制剂，IC50 为 1.1 nM。IC50 & Target IC50: 1.1 nM (RSK2) 1体外研究 BIX 02565, a potent RSK2 inhibitor (IC50=1.1 nM) targets for the treatment of heart failure secondary tomyocardial infarction through indirect NHE inhibition 1. BIX 02565, a second Rsk inhibitor, prote

5、cts enzymeactive sites from reaction with biotinylated nucleotide acyl phosphates 2.体内研究 In telemetry-instrumented rats, BIX 02565 (30, 100, and 300 mg/kg p.o. QD for 4 days) elicits concentration-dependent decreases in MAP after each dose (to -394 mm Hg on day 4 at Tmax). BIX 02565 producesconcentr

6、ation-dependent relaxation ex vivo in the phenylephrine-constricted rat aortic ring at concentrationsabove 0.03 M with a calculated EC50 of 3.1 M. Subsequently, BIX 02565 is infused in the anesthetized ratin a low-dose (0.1, 0.3, and 1.0 mg/kg per 20 min) and high-dose (1.0, 3.0, and 10.0 mg/kg per

7、20 min)series of continuous infusions to test the effect of compound on hemodynamics in vivo 1.PROTOCOLKinase Assay 1 Radioligand binding studies are performed at MDS Pharma Services. Mean percentage inhibition of specificbinding or activity is shown for each assay tested, and in selected assays (fo

8、r BIX 02565) when inhibition ofadrenergic binding generally exceeded 50%, an IC50 is determined by a nonlinear least-squares regressionanalysis. In brief, human RSK2 protein is used to measure kinase activity utilizing Kinase GloPlus that uses aluciferin-luciferase based detection reagent to quantif

9、y residual ATP. The relative light unit signal ismeasured on an LJL Analyst in luminescence mode using 384 aperture; relative light unit signals areconverted to percentage of control; the IC50 is fitted to a standard four-parameter logistic equation 1.MCE has not independently confirmed the accuracy

10、 of these methods. They are for reference only.Animal Rats 1Administration 1 Mean arterial pressure is assessed in conscious, freely moving male Sprague-Dawley rats (n=6/group)instrumented with telemetry transmitters. BIX 02565 (30, 100, and 300 mg/kg p.o. QD) is administered as asolution (10 mL/kg)

11、 in a 20% hydroxy-propyl-cyclodextran vehicle. Mean arterial pressure is reported from2 h before (baseline) and 90 h after the first dose; compound is administered at 0, 24, 48, and 72 h. A bloodsample is collected from satellite rats (n=3/group) at 1-h after dose (Tmax) on days 1 and 4 for analysis

12、 ofplasma drug concentrations by mass spectrometry.MCE has not independently confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献 Harvard Medical School LINCS LIBRARYSee more customer validations on HYPERLINK / www.MedChemEREFERENCES2/3 Master of Small Molecules 您边的抑制剂师ww

13、w.MedChemE1. Fryer RM, et al. Mitigation of off-target adrenergic binding and effects on cardiovascular function in the discovery of novel ribosomal S6kinase 2 inhibitors. Journal of Pharmacology and Experimental Therapeutics (2012), 340(3), 492-500.2. Edgar AJ, et al. A combination of SILAC and nucleotide acyl phosphate labelling reveals unexpected targets of the Rsk inhibitor BI-D1870. Biosci Rep. 2013 Dec 17.M