BAY-61-3606-dihydrochloride - Syk 抑制劑 - 生命科學(xué)試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEBAY 61-3606 dihydrochlorideCat. No.: HY-14985CAS No.: 648903-57-5分式: CHClNO分量: 463.32作靶點(diǎn): Syk作通路: Protein Tyrosine Kinase/RTK儲(chǔ)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(shí)驗(yàn) DMSO : 4.7 mg/mL (10.14

2、 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 2.1583 mL 10.7917 mL 21.5834 mL5 mM 0.4317 mL 2.1583 mL 4.3167 mL10 mM 0.2158 mL 1.0792 mL 2.1583 mL請(qǐng)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(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 BAY 61-3606 dihydrochloride種有效的，選擇性的，可

3、逆的，ATP 競(jìng)爭(zhēng)性的 Syk tyrosine kinase 抑制劑，IC50 值為 10 nM；對(duì) Btk，F(xiàn)yn，Itk，Lyn 和 Src 抑制作。IC50 & Target IC50: 10 nM (Syk)體外研究BAY 61-3606 inhibits the release of various inflammatory mediators in a concentration-dependent manner.1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEThe IC50 values for the FcRI-mediat

4、ed hexosaminidase release from a rat basophilic leukemia cell line,RBL-2H3, and serotonin release from rat peritoneal mast cells are found to be 46 and 17 nM,respectively. BAY 61-3606 inhibits FcRI-mediated histamine and tryptase release from HCMCs with IC50values of 5.1 and 5.5 nM, respectively, in

5、 a manner similar to its effect on the degranulation of RBL-2H3 cellsand rat peritoneal mast cells. BAY 61-3606 inhibits histamine release from leukocytes in high and low IgEgroups equipotently, giving IC50 values of 8.1 and 10 nM, respectively 1. BAY 61-3606 affects viability incells expressing mut

6、ant K-RAS or B-RAF through a MAPK-independent pathway. Inhibition of SYK is notresponsible for the BAY 61-3606 effect on cell viability in colorectal cancer cells. MAP4K2 is a target for BAY61-3606 that modulates the response of wild-type cells to AZ-628 2. BAY61-3606 has a 50% CytotoxicityConcentra

7、tion (CC50) value of greater than 100 M, and it inhibits AD169 replication 3.體內(nèi)研究 BAY 61-3606 (3, 10, 30, 100 mg/kg, p.o.) dose dependently inhibits the PCA reaction with an ED50 value of8 mg/kg. In a bronchoconstriction model, BAY 61-3606 dose dependently inhibits the DNP-BSA-inducedincrease in pul

8、monary pressure, and the dose of 3 mg/kg shows statistically significant suppression 1.PROTOCOLKinase Assay 1 GST-Syk (3.2 ng), 0.5 g AL, 30 M ATP, and testing compound in the presence of 0.25% Me2SO are mixedin 50 L/well of kinase assay buffer in polypropylene U-bottom 96-well microtiter plates. Th

9、e mixture isincubated for 1 h at room temperature, and the reaction is terminated by the addition of 120 L of terminationbuffer. To capture AL, 120 L of the terminated mixture is transferred to streptavidin-coated plates, followedby incubation at room temperature for more than 30 min. After three is

10、hes with washing buffer, 100 L ofantibody buffer is added and incubated at room temperature for more than 30 min. After three more ishes,100 L of enhancement solution is added. Time-resolved fluorescence is measured by multilabel counterARVO.MCE has not independently confirmed the accuracy of these

11、methods. They are for reference only.Cell Assay 3 HFF cells are seeded at a density of 1104 cells per well into 96-well plates. After 4 hours incubation to allowcell attachment, cells are treated for the time indicated in the text with different concentrations of eachcompound in duplicate. Cell viab

12、ility is then determined with an MTT assay according to the manufacturersprotocol. The final concentration of DMSO in all samples is maintained at 4 cells per well is included.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Rats: Rats are immuniz

13、ed by i.p. injection of OVA in Al(OH)3 suspension on days 0 and 14. On days 20 andAdministration 1 21, an aerosol of 1% OVA in saline is administered by inhalation. BAL fluid is collected, and cell number anddifferential counts are determined. BAY 61-3606 is administered (p.o.) from days 0 to 21 (b.

14、i.d.).Dexamethasone is administered (p.o.) from days 0 to 9 and days 18 to 21 (b.i.d.).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) Neuro Oncol. 2018 Apr 9;20(5):621-631. Front Immunol. 2018 Feb 15;9:249.2/3 Master of Small Molecules 您邊的抑

15、制劑師www.MedChemE Harvard Medical School LINCS LIBRARYSee more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Yamamoto N, et al. The orally available spleen tyrosine kinase inhibitor 2-7-(3,4-dimethoxyphenyl)-imidazo1,2-cpyrimidin-5-ylaminonicotinamide dihydrochloride (BAY 61-3606) block

16、s antigen-induced airway inflammation in rodents. J Pharmacol Exp Ther. 22. Lau KS, et al. BAY61-3606 affects the viability of colon cancer cells in a genotype-directed manner. PLoS One. 2012;7(7):e41343.3. Ho CM, et al. Inhibition of IKK by BAY61-3606 Reveals IKK-Dependent Histone H3 Phosphorylation in Human CytomegalovirusInfected C