Fostamatinib (R788)

製品コードS2625 バッチS262501

印刷

化学情報

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

C23H26FN6O9P
分子量 580.46 CAS No. 901119-35-5
Solubility (25°C)* 体外 DMSO 116 mg/mL (199.84 mM)
Water Insoluble
Ethanol 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 Fostamatinib (R788), a prodrug of the active metabolite R406, is a Syk inhibitor with IC50 of 41 nM, strongly inhibits Syk but not Lyn, 5-fold less potent to Flt3. Phase 3.
in vitro Fostamatinib (R788) is a prodrug of the spleen tyrosine kinase (Syk) inhibitor R406. It is a competitive inhibitor for ATP binding with a Ki of 30 nM, and dose-dependently inhibits anti-IgE-mediated CHMC degranulation with an EC50 of 56 nM. This compound also inhibits the anti-IgE-induced production and release of LTC4 and cytokines and chemokines, including TNFα, IL-8, and GM-CSF. Inhibition of Syk by R788 results in inhibition of all phosphorylation events downstream of Syk signaling. Next to FcϵRI signaling in CHMC, it most potently inhibits the signaling of IL-4 and IL-2 receptors. R788 specifically inhibits FcγR signaling in human mast cells, macrophages, and neutrophils, and can inhibit local inflammatory injury mediated by immune complexes. [1] It induces apoptosis of the majority of examined DLBCL cell lines. In R788-sensitive DLBCL cell lines, this compound specifically inhibits both tonic- and ligand-induced BCR signaling (autophosphorylation of SYK525/526 and SYK-dependent phosphorylation of the B-cell linker protein [BLNK]). [2]
in vivo Oral administration of Fostamatinib (R788) to mice reduces immune complex-mediated inflammation in a reverse-passive Arthus reaction and two antibody-induced arthritis models. [1] In another study, it effectively inhibits BCR signaling in vivo, resulting in reduced proliferation and survival of the malignant B cells and significantly prolongs survival of the treated animals. [3] This compound demonstrates a significant reduction in major inflammatory mediators such as TNFalpha, IL-1, IL-6 and IL-18, leading to reduced inflammation and bone degradation in models of rheumatoid arthritis. [4]
特徴 Converted into its active metabolite R406 in vivo.

プロトコル(参考用のみ)

キナーゼアッセイ Fluorescence polarization kinase assay and Ki determination
The fluorescence polarization reactions are performed. For Ki determination, 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 Fostamatinib (R788) 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 this compound, 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 Ki/Vmax) is plotted against the inhibitor concentration to determine the Ki.
細胞アッセイ 細胞株 Cultured human mast cells (CHMC)
濃度 0 μM -100 μM
反応時間 30 minutes
実験の流れ

Before stimulation with either 0.25 to 2 mg/mL anti-IgE or anti-IgG or 2 µM ionomycin, cells are incubated with Fostamatinib (R788) or DMSO for 30 minutes. Cultured human mast cells (CHMC) are derived from cord blood CD34+ progenitor cells and grown, primed, and stimulated and shown in supplemental data. For tryptase measurement, ∼1500 cells per well are stimulated for 30 min in modified Tyrode's buffer. For LTC4 and cytokine production, 100,000 cells per well are stimulated for 1 or 7 hours, respectively. Tryptase activity is measured by luminescence readout of a peptide substrate, and LTC4 and cytokines are measured using Luminex multiplex technology.
動物実験 動物モデル Balb/c mice with arthritis
投薬量 1 mg/kg or 5 mg/kg
投与方法 Orally b.i.d

参考

  • https://pubmed.ncbi.nlm.nih.gov/16946104/
  • https://pubmed.ncbi.nlm.nih.gov/18006696/
  • https://pubmed.ncbi.nlm.nih.gov/20716772/
  • https://pubmed.ncbi.nlm.nih.gov/19333898/

カスタマーフィードバック

Data from [Data independently produced by , , Haematologica, 2016 Feb, 101(2): e59–e62.]

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：

R406 and its structural analogs reduce SNCA/α-synuclein levels via autophagic degradation [ Autophagy, 2025, 1-17.] PubMed: 40143425
Spleen tyrosine kinase aggravates intestinal inflammation through regulating inflammatory responses of macrophage in ulcerative colitis [ Int Immunopharmacol, 2025, 148:114122] PubMed: 39862635
Repurposing of the Syk inhibitor fostamatinib using a machine learning algorithm [ Exp Ther Med, 2025, 29(6):110] PubMed: 40242601
CpG oligonucleotides induce an acute murine thrombocytopenia dependent on toll-like receptor 9 and spleen tyrosine kinase pathways [ J Thromb Haemost, 2024, S1538-7836(24)00479-3] PubMed: 39155024
A semiconductor 96-microplate platform for electrical-imaging based high-throughput phenotypic screening [ Nat Commun, 2023, 14(1):7576] PubMed: 37990016
TLR7/8 stress response drives histiocytosis in SLC29A3 disorders [ J Exp Med, 2023, 220(9)e20230054] PubMed: 37462944
TLR7/8 stress response drives histiocytosis in SLC29A3 disorders [ J Exp Med, 2023, 220(9)e20230054] PubMed: 37462944
Syk Inhibition Reprograms Tumor-Associated Macrophages and Overcomes Gemcitabine-Induced Immunosuppression in Pancreatic Ductal Adenocarcinoma [ Cancer Res, 2023, 83(16):2675-2689] PubMed: 37306759
Syk-dependent alternative homologous recombination activation promotes cancer resistance to DNA targeted therapy [ Res Sq, 2023, rs.3.rs-2922520] PubMed: 37333340
Blockade of Syk modulates neutrophil immune-responses via the mTOR/RUBCNL-dependent autophagy pathway to alleviate intestinal inflammation in ulcerative colitis [ Precis Clin Med, 2023, 10.1093/pcmedi/pbad025] PubMed: 37941642

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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