Fostamatinib

SKU: orb1301060

Description

Fostamatinib (R788) is a prodrug metabolized to the active Syk inhibitor R406, exhibiting an IC50 of 41 nM against Syk while showing no activity against Lyn. This inhibitor is utilized in research on immunology and oncology, with applications in both in vitro signaling studies and in vivo models of autoimmune and inflammatory diseases.

Research Area

Cardiovascular Research, Neuroscience, Pharmacology & Drug Discovery, Signal Transduction

Key Properties

• CAS Number: 901119-35-5
• MW: 580.46
• Purity: 99.38% (May vary between batches)
• Formula: C₂₃H₂₆FN₆O₉P
• SMILES: COc1cc(Nc2ncc(F)c(Nc3ccc4OC(C)(C)C(=O)N(COP(O)(O)=O)c4n3)n2)cc(OC)c1OC
• Target: Adenosine Receptor,Syk,FLT,Monoamine Transporter
• Solubility: DMSO:127.5 mg/mL (219.65 mM);Ethanol:< 1 mg/mL (insoluble or slightly soluble);10% DMSO+40% PEG300+5% Tween 80+45% Saline:4 mg/mL (6.89 mM);H2O:< 1 mg/mL (insoluble or slightly soluble)

Bioactivity

• Target IC50:
  Syk:41 nM|Lck:37 nM|Lyn:63 nM|Syk/FLT3:30 nM (Ki)
• In Vivo:
  In human adipocytes, macrophages, and neutrophils, Fostamatinib specifically inhibits FcγR signaling. It induces apoptosis in most DLBCL cell lines. Fostamatinib (EC50=56 nM) inhibits anti-IgE mediated CHMC degranulation in a dose-dependent manner. Additionally, it inhibits the production and release of LTC4, cytokines, and chemokines, including TNFα, IL-8, and GM-CSF, induced by anti-IgE.
• In Vitro:
  In rheumatoid arthritis models, Fostamatinib significantly reduces inflammatory mediators such as TNF-alpha, IL-1, IL-6, and IL-18, thereby diminishing inflammation and bone degeneration. It effectively inhibits BCR signaling in vivo, leading to decreased proliferation and survival of malignant B cells, and notably prolongs the survival of treated animals. Oral administration of Fostamatinib in reverse passive Arthus reaction and dual-antibody-induced arthritis mouse models reduces immune complex-mediated inflammation.
• Cell Research:
  Cultured human mast cells (CHMC) are derived from cord blood CD34+ progenitor cells and grown, primed, and stimulated and shown in supplemental data. Before stimulation, cells are incubated with R788 or DMSO for 30 minutes. Cells are then stimulated with either 0.25 to 2 mg/mL anti-IgE or anti-IgG or 2 μM ionomycin. 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. (Only for Reference)

Storage & Handling

• Storage: store at low temperature,keep away from moisture | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

inhibit, Inhibitor, FLT3, Fms like tyrosine kinase 3, Fostamatinib, MonoamineTransporter, Monoamine Transporter, Monoamine transporter, A3, AdenosineReceptor, Adenosine transporter, Adenosine Receptor, CD135, Cluster of differentiation antigen 135, R 788, R788, R-788, Syk, Spleen tyrosine kinase

Compound Identifiers

PubChem CID

11671467