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
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <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. This compound inhibits the anti-IgE-induced production and release of LTC4 and cytokines and chemokines, including TNFα, IL-8, and GM-CSF. It inhibits phosphorylation of Syk substrate linker for activation of T cells in mast cells and B-cell linker protein/SLP65 in B cells. This chemical binds to the ATP binding pocket of Syk and inhibits its kinase activity as an ATP-competitive inhibitor with Ki of 30 nM. It blocks Syk-dependent FcR-mediated activation of monocytes/macrophages and neutrophils and Bcr-mediated activation of B lymphocytes. [1]

This compound 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]

It 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. This compound also shows efficacy in inhibiting paw inflammation in antibody-induced arthritis mouse models. [1]

It 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, this compound 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

参考

  • https://pubmed.ncbi.nlm.nih.gov/16946104/
  • https://pubmed.ncbi.nlm.nih.gov/19491390/
  • https://pubmed.ncbi.nlm.nih.gov/21848694/
  • https://pubmed.ncbi.nlm.nih.gov/17490694/

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：

Bruton's tyrosine kinase (BTK) and matrix metalloproteinase-9 (MMP-9) regulate NLRP3 inflammasome-dependent cytokine and neutrophil extracellular trap responses in primary neutrophils [ J Allergy Clin Immunol, 2025, 155(2):569-582] PubMed: 39547282
Dectin-1 is Pathogenic in Chronic Kidney Disease by Promoting Macrophage Infiltration and Transition to Myofibroblast [ Int J Biol Sci, 2025, 21(12):5287-5304] PubMed: 40959267
TREM-1 as a potential gatekeeper of neuroinflammatory responses: therapeutic validation and mechanistic insights in experimental traumatic brain injury [ Front Immunol, 2025, 16:1636917] PubMed: 40761800
Spleen tyrosine kinase inhibitors disrupt human neutrophil swarming and antifungal functions [ Microbiol Spectr, 2025, 13(1):e0254921] PubMed: 39601545
Aberrant METTL1-mediated tRNA m7G modification alters B-cell responses in systemic autoimmunity in humans and mice [ Nat Commun, 2024, 15(1):10599] PubMed: 39638793
Centrioles are frequently amplified in early B cell development but dispensable for humoral immunity [ Nat Commun, 2024, 15(1):8890] PubMed: 39406735
Egfl6 promotes ovarian cancer progression by enhancing the immunosuppressive functions of tumor-associated myeloid cells [ J Clin Invest, 2024, e175147] PubMed: 39312740
Galectin-3 induces pathogenic immunosuppressive macrophages through interaction with TREM2 in lung cancer [ J Exp Clin Cancer Res, 2024, 43(1):224] PubMed: 39135069
Tuning the Immune Cell Response through Surface Nanotopography Engineering [ Small Sci, 2024, 4(9):2400227] PubMed: 40212066
CD22 blockade exacerbates neuroinflammation in Neuromyelitis optica spectrum disorder [ J Neuroinflammation, 2024, 21(1):313] PubMed: 39616380

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。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。