Peficitinib-ASP015K-DataSheet-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEPeficitinibCat. No.: HY-19568CAS No.: 944118-01-8Synonyms: ASP015K; JNJ-54781532分式: CHNO分量: 326.39作靶點(diǎn): JAK作通路: Epigenetics; JAK/STAT Signaling; Stem Cell/Wnt儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶

2、解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 60 mg/mL (183.83 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 3.0638 mL 15.3191 mL 30.6382 mL5 mM 0.6128 mL 3.0638 mL 6.1276 mL10 mM 0.3064 mL 1.5319 mL 3.0638 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 Pefici

3、tinib種可服的 JAK 抑制劑，對(duì) JAK1，JAK2，JAK3 和 Tyk2 的 IC50 值分別為 3.9，5.0，0.7 和 4.8nM。IC50 & Target JAK3 JAK1 Tyk2 JAK20.7 nM (IC50) 3.9 nM (IC50) 4.8 nM (IC50) 5 nM (IC50)1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE體外研究 Peficitinib is an oral JAK inhibitor, with IC50s of 3.9, 5.0, 0.7 and 4.8 nM for JAK1,

4、 JAK2, JAK3 and Tyk2,respectively. Peficitinib inhibits IL-2-induced T cell proliferation with an IC50 of 10 nM. Peficitinib alsosuppresses the IL-2-induced STAT5 phosphorylation in rat and human whole blood, with mean IC50s of 124nM and 127 nM, respectively 1.體內(nèi)研究 Peficitinib (20 mg/kg, p.o.) suppr

5、esses IL-2-induced STAT5 phosphorylation by 78% in the rat model ofadjuvant-induced arthritis (AIA). Peficitinib potently inhibits the increase in paw volume (1 mg/kg) with anED50 of 2.7 mg/kg, significantly reduces the bone destruction score (10 mg/kg) and almost fully amelioratesboth paw swelling

6、and bone destruction scores (30 mg/kg) 1.PROTOCOLKinase Assay 1 Human JAK1, JAK2, JAK3, TYK2-domains assays performed using streptavidin-coated 96-well plates.Reaction mixture contained 15 mM Tris-HCl (pH 7.5), 0.01% Tween 20, 2 mM dithiothreitol, 10 mM MgCl2,250 nM Biotin-Lyn-Substrate-2 (for JAK1,

7、 2 and 3) or Biotin-IRS1-Substrate (for TYK2), and ATP (at finalconcentrations of 200 M JAK1, 10 M JAK2, 8 M JAK3, and 4 M TYK2). Peficitinib or tofacitinib isdissolved in DMSO. The reaction is initiated by adding the kinase domain, followed by incubation at roomtemperature for 1 h. Kinase activity

8、is measured as the rate of phosphorylation of Biotin-Lyn-Substrate-2 orBiotin-IRS-Substrate using HRP-conjugated anti-phosphotyrosine antibody (HRP-PY-20) using aphosphotyrosine-specific ELISA. TYK2 kinase assay of Peficitinib is performed with the ATP concentration of10 M 1.MCE has not independentl

9、y confirmed the accuracy of these methods. They are for reference only.Cell Assay 1 Splenocytes from male Lewis rats are suspended in RPMI1640 supplemented with 10% fetal bovine serumand 50 M 2-mercaptoethanol at a density of 1.5 106 cells/mL. Rat splenocytes are cultured withConcanavalin A for 24 h

10、 at 37C to induce IL-2 receptor expression. Splenocytes are then incubated with IL-2and Peficitinib or tofacitinib at designated concentrations in 96-well tissue culture plates. After 3-dayincubation, alamarBlue is added to each of the test wells, followed by 4-6 h incubation. Fluorescenceintensity

11、is measured at an excitation wavelength of 545 nm and an emission wavelength of 590 nm. Allexperiments are performed in triplicate, and experiments are performed either four times or once for assaysusing Peficitinib or tofacitinib, respectively. For each individual, wells cultured with cells and med

12、ium aloneare prepared for the blanks, and IL-2 stimulated cells without JAK inhibitors are prepared for the controls. Tocalculate the % inhibition of JAK inhibitors, blanks and controls are designated as 100% and 0% inhibition,respectively 1.MCE has not independently confirmed the accuracy of these

13、methods. They are for reference only.Animal Rats 1Administration 1 Seven-weeks-old female Lewis rats are used for the adjuvant-induced arthritis (AIA) model. Body weight andleft hind paw volume of each rat are measured (MK-101PR volume meter), and the values are used to assignanimals to one of six g

14、roups (n = 10). Arthritis is induced on day 0 in five of these groups by injecting asuspension of Mycobacterium tuberculosis H37 RA strain (0.5 mg/rat) in liquid paraffin into the right hind footpad. The remaining group is not injected with adjuvant (normal group, n = 10). For the oral administratio

15、nregimen, four of the adjuvant-injected groups receive Peficitinib (1, 3, 10, and 30 mg/kg) dissolved in 0.5%2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEmethylcellulose (MC) once daily. Rats in the normal and control groups receive 0.5% MC alone 1.MCE has not independently confirmed the accurac

16、y of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Cells. 2019 Jun 9;8(6). pii: E561. Cancer Manag Res. 2018 Dec 28;11:389-399.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Ito M, et al. A novel JAK inhibitor, peficitinib, demonstrates potent efficacy in a rat adjuvant-induced arthritis mode