Fostamatinib (R788)

Catalog No.S2625

For research use only.

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.

Fostamatinib (R788) Chemical Structure

CAS No. 901119-35-5

Selleck's Fostamatinib (R788) has been cited by 28 publications

Purity & Quality Control

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Biological Activity

Description 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.
Features Converted into its active metabolite R406 in vivo.
Targets
Syk [1] Adenosine A3 receptor [1] Adenosine transporter [1] Monoamine transporter [1]
41 nM 81 nM 1.84 μM 2.74 μM
In vitro

R788 is a prodrug of the spleen tyrosine kinase (Syk) inhibitor R406. R788 is a competitive inhibitor for ATP binding with a Ki of 30 nM. R788 dose-dependently inhibits anti-IgE-mediated CHMC degranulation with an EC50 of 56 nM. R788 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, R788 most potently inhibits the signaling of IL-4 and IL-2 receptors. R788 specifically inhibits FcγR signaling in human mast cells, macrophages, and neutrophils. R788 can inhibit local inflammatory injury mediated by immune complexes. [1] R788 induces apoptosis of the majority of examined DLBCL cell lines. In R788-sensitive DLBCL cell lines, R788 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]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
human Ramos cells NGfRcFZHfW6ldHnvckBie3OjeR?= NIrt[ItKdmirYnn0bY9vKG:oIGPZT{BqdiCqdX3hckBT[W2xczDj[YxteyxiSVO1NF0xNjJ4NzFOwG0> NEX4RoQzOzN3MEi0Oy=>
In vivo Oral administration of R788 to mice reduces immune complex-mediated inflammation in a reverse-passive Arthus reaction and two antibody-induced arthritis models. [1] In another study, R788 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] R788 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]

Protocol (from reference)

Kinase Assay:

[1]

  • 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 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 R788, 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.

Cell Research:

[1]

  • Cell lines: Cultured human mast cells (CHMC)
  • Concentrations: 0 μM -100 μM
  • Incubation Time: 30 minutes
  • Method:

    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)
Animal Research:

[1]

  • Animal Models: Balb/c mice with arthritis
  • Dosages: 1 mg/kg or 5 mg/kg
  • Administration: Orally b.i.d
  • (Only for Reference)

Solubility (25°C)

In vitro

DMSO 116 mg/mL
(199.84 mM)
Water Insoluble
Ethanol Insoluble

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
4% DMSO+30% PEG 300+ddH2O
For best results, use promptly after mixing.

5mg/mL

* 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.

Chemical Information

Molecular Weight 580.46
Formula

C23H26FN6O9P

CAS No. 901119-35-5
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CC1(C(=O)N(C2=C(O1)C=CC(=N2)NC3=NC(=NC=C3F)NC4=CC(=C(C(=C4)OC)OC)OC)COP(=O)(O)O)C

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

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Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

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Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT04543279 Recruiting Drug: Fostamatinib|Drug: Ruxolitinib Myelofibrosis Washington University School of Medicine|Rigel Pharmaceuticals May 3 2021 Phase 2
NCT04904276 Recruiting Drug: Fostamatinib ITP|Immune Thrombocytopenia Rigel Pharmaceuticals May 18 2021 --
NCT02611063 Active not recruiting Drug: fostamatinib Hematological Malignancies Stefanie Sarantopoulos MD PhD.|Duke University January 2016 Phase 1
NCT01725230 Completed Drug: Fostamatinib|Drug: Rosuvastatin|Drug: Simvastatin Rheumatoid Arthritis AstraZeneca November 2012 Phase 1
NCT01608542 Completed Drug: Fostamatinib 100mg|Drug: Fostamatinib 200mg Healthy Japanese Volunteers AstraZeneca June 2012 Phase 1

(data from https://clinicaltrials.gov, updated on 2022-01-17)

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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Frequently Asked Questions

Question 1:
What’s the difference between S2625 and S2206?

Answer:
S2206 is more stable than S2625. The water solubility of S2206 is better than S2625. The absorption of S2206 is harder than S2625, so you need to test the suitable dosage if you use the product in animal assays. The potency of S2206 and S2625 is similar.

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