R406

製品コードS2194 バッチS219403

印刷

化学情報

Chemical Structure Synonyms R406 besylate Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C22H23FN6O5.C6H6O3S
分子量 628.63 CAS No. 841290-81-1
Solubility (25°C)* 体外 DMSO 126 mg/mL (200.43 mM)
Ethanol 8 mg/mL (12.72 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 R406(R406 besylate) is a potent Syk inhibitor with IC50 of 41 nM in cell-free assays, strongly inhibits Syk but not Lyn, 5-fold less potent to Flt3. R406 induces apoptosis. Phase 1.
in vitro

R406 is a potent inhibitor of immunoglobulin E (IgE)- and IgG-mediated activation of Fc receptor signaling. R406 inhibits the anti-IgE-induced production and release of LTC4 and cytokines and chemokines, including TNFα, IL-8, and GM-CSF. R406 inhibits phosphorylation of Syk substrate linker for activation of T cells in mast cells and B-cell linker protein/SLP65 in B cells. R406 binds to the ATP binding pocket of Syk and inhibits its kinase activity as an ATP-competitive inhibitor with Ki of 30 nM. R406 blocks Syk-dependent FcR-mediated activation of monocytes/macrophages and neutrophils and Bcr-mediated activation of B lymphocytes. [1]

R406 significantly induces chronic lymphocytic leukemia (CLL) cell apoptosis in nurselike cells cocultures and blocks CCL3 and CCL4 secretion by CLL cells in response to B-cell antigen receptor (Bcr) triggering. [2]

R406 is a potent inhibitor of platelet signaling and functions initiated by FcγRIIA cross-linking by specific antibodies or by sera from HIT patients. [3]
in vivo

R406 reduces cutaneous reverse passive Arthus reaction by approximately 86% at 5 mg/kg in prophylactic treated mice. R406 also shows efficacy in inhibiting paw inflammation in antibody-induced arthritis mouse models. [1]

R406 does not adversely affect macrophage or neutrophil function in innate immune responses and has minimal functional immunotoxicity notwithstanding its lymphocytopenic effect. [4]
特徴 Lead drug candidate for rheumatoid arthritis.

プロトコル(参考用のみ)

キナーゼアッセイ In Vitro Fluorescence Polarization Kinase Assay
R406 is serially diluted in DMSO and then diluted to 1% DMSO in kinase buffer (20 mM HEPES, pH 7.4, 5 mM MgCl2, 2 mM MnCl2, 1 mM DTT, 0.1 mg/mL acetylated BGG). ATP and substrate in kinase buffer are added at room temperature, resulting in a final DMSO concentration on 0.2%. The kinase reactions are performed in a final volume of 20 mL containing 5mM HS1 peptide substrate, 4 mM ATP and started by addition of 0.125 ng of Syk in kinase buffer. The reaction is allowed to proceed for 40 minutes at room temperature. The reaction is stopped by the addition of 20 mL of PTK quench mix containing EDTA/anti-phosphotyrosine antibody (1X final)/fluorescent phosphopeptide tracer (0.5X final) diluted in FP Dilution Buffer. The plate is incubated for 30 minutes in the dark at room temperature and then read on a Polarion fluorescence polarization plate reader. Data are converted to amount of phosphopeptide present using a calibration curve generated by competition with the phosphopeptide competitor provided in the Tyrosine Kinase Assay Kit. For IC50 determination, R406 is tested at eleven concentrations and curve-fitting is performed by non-linear regression analysis.
細胞アッセイ 細胞株 Cultured human mast cells
濃度 30 nM
反応時間
実験の流れ

Cells were treated with different concentrations of R406.
動物実験 動物モデル Arthritis is induced in C57BL/6 mice by intraperitoneal injection of 150 μL of pooled sera from adult K/BxN mice.
投薬量 1 or 5 mg/kg
投与方法 Administered orally

カスタマーフィードバック

Data from [Data independently produced by Blood, 2014, 122(4), 580-9]

Data from [Data independently produced by J Clin Invest, 2014, 124(11), 5074-84]

Data from [Data independently produced by PLoS One, 2014, 9(5), e96703]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Bactericidal/permeability-increasing protein instructs dendritic cells to elicit Th22 cell response [ Cell Rep, 2024, 43(3):113929] PubMed: 38457343
B1-cell-produced anti-phosphatidylserine antibodies contribute to lupus nephritis development via TLR-mediated Syk activation [ Cell Mol Immunol, 2023, 1-14.] PubMed: 37291237
Loss of NF1 in Melanoma Confers Sensitivity to SYK Kinase Inhibition [ Cancer Res, 2023, 83(2):316-331] PubMed: 36409827
Adjuvant activity of tubeimosides by mediating the local immune microenvironment [ Front Immunol, 2023, 14:1108244] PubMed: 36845089
Integrated single-cell (phospho-)protein and RNA detection uncovers phenotypic characteristics and active signal transduction of human antibody secreting cells [ Mol Cell Proteomics, 2023, S1535-9476(23)00001-4] PubMed: 36623694
Dual RNA-Sequencing and Liquid Chromatography-Mass Spectrometry Unveil Specific Insights on the Pathogenicity of Trichophyton mentagrophytes Complex [ J Invest Dermatol, 2023, 143(3):470-479.e6] PubMed: 38295003
Multiparametric Profiling of Neutrophil Function via a High-Throughput Flow Cytometry-Based Assay [ Cells, 2023, 12(5)743] PubMed: 36899878
Endothelial TREM-1 receptor regulates the blood-brain barrier integrity after intracerebral hemorrhage in mice via SYK/β-catenin signaling [ CNS Neurosci Ther, 2023, 10.1111/cns.14255] PubMed: 37170484
Toll-like receptor 4 and Syk kinase shape dendritic cell-induced immune activation to major house dust mite allergens [ Front Med (Lausanne), 2023, 10:1105538] PubMed: 37614946
Toll-like receptor 4 and Syk kinase shape dendritic cell-induced immune activation to major house dust mite allergens [ Front Med (Lausanne), 2023, 10:1105538] PubMed: 37614946

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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