841290-81-1

841290-81-1 structure

Name: R406
Chemical Name: benzenesulfonic acid,6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one
CAS Number: 841290-81-1
Molecular Formula: C₂₈H₂₉FN₆O₈S
Molecular Weight: 628.629
Catalog: Biochemical Inhibitor Angiogenesis Syk inhibitor
Create Date: 2018-06-19 18:19:11
Modify Date: 2024-01-02 21:26:18
R406 is a competitive Syk inhibitor for ATP binding with a Ki of 30 nM, potently inhibits Syk kinase activity in vitro with an IC50 of 41 nM, measured at an ATP concentration corresponding to its Km value.

Name	benzenesulfonic acid,6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one
Synonyms	CS-0229 6-({5-Fluoro-2-[(3,4,5-trimethoxyphenyl)amino]-4-pyrimidinyl}amino)-2,2-dimethyl-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one benzenesulfonate (1:1) R406-Supplied by Selleck Chemicals S2194_Selleck R406 2H-Pyrido[3,2-b]-1,4-oxazin-3(4H)-one, 6-[[5-fluoro-2-[(3,4,5-trimethoxyphenyl)amino]-4-pyrimidinyl]amino]-2,2-dimethyl-, benzenesulfonate (1:1)

Description	R406 is a competitive Syk inhibitor for ATP binding with a Ki of 30 nM, potently inhibits Syk kinase activity in vitro with an IC50 of 41 nM, measured at an ATP concentration corresponding to its Km value.
Related Catalog	Signaling Pathways >> Protein Tyrosine Kinase/RTK >> Syk
Target	Ki: 30 nM (Syk)[1] IC50: 41 nM (Syk)[1]
In Vitro	R406 also exhibits antagonistic activity for adenosine A3 receptor with an IC50 estimated to be 93 nM[1]. In Ramos B lymphoma cells, B-cell receptor (BCR) crosslinking induces robust phosphorylation of B-cell linker protein (BLNK), which is ablated by addition of the Syk inhibitor R406. Additionally, R406 significantly reduces constitutive Syk signaling in EBV+ cell lines derived from patients with Post-transplant lymphoproliferative disorder (PTLD), termed SLCL. Therefore, R406 inhibits Syk activation[2].
In Vivo	Prophylactic treatment of mice with R406 administers 1 h before immune complex challenge reduces the cutaneous reverse passive Arthus reaction by approximately 72 and 86% at 1 and 5 mg/kg, respectively, compared with the vehicle control. The net optical density reading of extravasated dye extracted after treatment with R406 at 1 or 5 mg/kg R406 is reduced from 0.14 (vehicle) to 0.04 or 0.02, respectively (p<0.01)[1].
Kinase Assay	The fluorescence polarization reactions are performed. For Kidetermination, duplicate 200 μL reactions are set up at eight different ATP concentrations from 200 μM (2-fold serial dilutions) in the presence of either DMSO or R406 at 125, 62.5, 31.25, 15.5, or 7.8 nM. At different time points, 20 μL of each reaction is removed and quenched to stop the reaction. For each concentration of R406, the rate of reaction at each concentration of ATP is determined and plotted against the ATP concentration to determine the apparent Km and Vmax (maximal rate). Finally the apparent Km (or apparent Km/Vmax) is plotted against the inhibitor concentration to determine the Ki. All data analysis is performed using Prism and Prism enzyme kinetics programs[1]
Cell Assay	Cells (0.5-1×106 cells/mL) are plated in serial dilutions of small molecule inhibitors R406, LY294002, or PD98059 (0-10 μM), or equivalent amounts of vehicle (DMSO, 0-1:1000). Drug and media are replenished after 48 h of a total of 96 h in culture at 37°C. Cell cycle analysis using propidium iodide. The percentage of apoptotic cells is determined using Annexin V-enhanced GFP (EGFP) apoptosis detection kits. Data is analyzed on a FACScan flow cytometer[2].
Animal Admin	Mice[1] Mice are challenged intravenously with 1% ovalbumin (OVA) in saline (10 mg/kg) containing 1% Evans blue dye. Ten minutes later, mice are anesthetized with isofluorane and shaved dorsolaterally. The rabbit anti-OVA IgG (50 μg/25 μL) is injected intradermally on the left side of the back at three adjacent locations. Three injections of rabbit polyclonal IgG (50 μg/25 μL) on the opposite side of the same animal served as controls. R406 (1 and 5 mg/kg) or vehicle (67% PEG 400) is administered to animals 60 min before antibody/antigen challenge. Four hours after challenge, the animals are euthanized, and skin tissue is assessed for edema and inflammation by measuring dye extravasation into the surrounding tissue. Punch biopsy of the injection sites (8 mm) are incubated in 2 mL of formamide at 80°C overnight. The concentration of the extravasated Evans blue dye is measured spectrophotometrically at OD610.
References	[1]. Braselmann S, et al. R406, an orally available spleen tyrosine kinase inhibitor blocks fc receptor signaling and reduces immune complex-mediated inflammation. J Pharmacol Exp Ther, 2006, 319(3), 998-1008. [2]. Hatton O, et al. Syk-induced phosphatidylinositol-3-kinase activation in Epstein-Barr virus posttransplant lymphoproliferative disorder. Am J Transplant. 2013 Apr;13(4):883-90. [3]. Kitai M, et al. Effects of a spleen tyrosine kinase inhibitor on progression of the lupus nephritis in mice. J Pharmacol Sci. 2017 May;134(1):29-36.

Molecular Formula	C₂₈H₂₉FN₆O₈S
Molecular Weight	628.629
Exact Mass	628.175171
PSA	198.22000
LogP	5.22730
Storage condition	-20℃

Hazard Codes	N