BIX-02565 - Ribosomal S6 Kinase (RSK) 抑制劑 - 生命科學(xué)試劑 - 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作靶點(diǎn): 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 : 20.75 mg/mL (45.25 mM; N

2、eed ultrasonic and warming)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液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請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。體內(nèi)實驗 請根據(jù)您的實驗動物和給藥式選擇適當(dāng)?shù)娜芙獍福渲魄罢埾扰渲瞥吻宓膬湟?，再依次添加助溶?為保證實驗結(jié)果的可靠性，體內(nèi)實驗的作液，建議您現(xiàn)現(xiàn)配，當(dāng)

3、天使；澄清的儲備液可以根據(jù)儲存條件，適當(dāng)保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 1.67 mg/mL (3.64 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 1.67 mg/mL (3.64 mM); Clear solutionBIOLOGICAL ACTIVITY1/3 Master of Small Molecules 您邊的抑制劑師www.Med

4、ChemE物活性 BIX 02565種有效的核糖體 S6 激酶 2 (RSK2) 抑制劑，IC50 為 1.1 nM。IC50 & Target IC50: 1.1 nM (RSK2) 1體外研究 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.體內(nèi)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.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Harvard Medical School LINCS LIBRARYSee more customer validations on HYPERLINK / www.MedChemEREFERENCES2/3 Master of Small Molecules 您邊的抑制劑師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