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Chemical Structure| 1025687-58-4 Chemical Structure| 1025687-58-4

Structure of Fostamatinib Disodium
CAS No.: 1025687-58-4

Chemical Structure| 1025687-58-4

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R788 disodium, the disodium form of R788, is a Syk inhibitor with IC50 of 41 nM.

Synonyms: R935788; NSC 745942; Fostamatinib

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Product Citations

Nanae Asakawa ; Toshiaki Oharaseki ; Yuki Yokouchi ; Noriko Miura ; Naohito Ohno ; Kei Takahashi

Abstract: Background: The activation of innate immunity may be involved in the development of Candida albicans-induced murine vasculitis, which resembles Kawasaki disease (KD)vasculitis. This study aimed to histologically clarify the time course of the development of vasculitis in this model in detail and to estimate the potential role of spleen tyrosine kinase (Syk) inhibitors in KD vasculitis. Methods and Results: DBA/2 male mice were intraperitoneally injected with a vasculitis_x005f_x0002_inducing substance and treated with a Syk inhibitor (R788 or GS-9973). Systemic vasculitis, especially in the aortic annulus area, was histologically evaluated. Regarding lesions in the aortic annulus area, some mice in the untreated control group already showed initiation of vasculitis 1 day after the final injection of a vasculitis-inducing substance. The vasculitis expanded over time. Inflammation occurred more frequently at the aortic root than at the coronary artery. The distribution of inflammatory cells was limited to the intima, intima plus adventitia, or all layers. In the Syk inhibitor-treated groups, only one mouse had vasculitis at all observation periods. The severity and area of the vasculitis were reduced by both Syk inhibitors. Conclusion: Candida albicans-induced murine vasculitis may occur within 1 day after the injection of a vasculitis-inducing substance. Additionally, Syk inhibitors suppress murine vasculitis.

Keywords: Kawasaki disease ; vasculitis ; Candida albicans ; murine model ; Syk

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Product Details of Fostamatinib Disodium

CAS No. :1025687-58-4
Formula : C23H24FN6Na2O9P
M.W : 624.42
SMILES Code : O=C1N(COP([O-])([O-])=O)C2=NC(NC3=NC(NC4=CC(OC)=C(OC)C(OC)=C4)=NC=C3F)=CC=C2OC1(C)C.[Na+].[Na+]
Synonyms :
R935788; NSC 745942; Fostamatinib
MDL No. :MFCD15146370
InChI Key :HSYBQXDGYCYSGA-UHFFFAOYSA-L
Pubchem ID :25008120

Safety of Fostamatinib Disodium

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of Fostamatinib Disodium

RTK

Isoform Comparison

Biological Activity

Target
  • Syk

    Syk, IC50:41 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
Neutrophils 1 μM 1 hour To evaluate the effect of R406 on LPS-induced degranulation and cytokine release in neutrophils, results showed that R406 significantly reduced degranulation but had minimal impact on cytokine release PMC11387147
Mouse platelets 1 µM 10 minutes To validate the inhibitory effect of Fostamatinib on platelet signaling, results showed that R406 significantly reduced the activation of Syk and Src family kinases. PMC10768010
Healthy donor washed human platelets 10 µM 10 minutes R406 completely abolished the tyrosine phosphorylation of Syk, LAT, and PLCγ2 induced by atherosclerotic plaque homogenate and blocked upstream Src Y418 autophosphorylation at 10 μM concentration. PMC9266367
Healthy donor washed human platelets 3 µM 10 minutes R406 at 3 μM concentration significantly inhibited platelet aggregation in response to 70 μg/mL of plaque homogenate and completely blocked platelet aggregation in washed platelets at 10 μM concentration. PMC9266367
Neutrophils 0.25, 0.5, 1 μM 2 h Reduced LPS-induced neutrophil activation and ROS release PMC11606345
BMDMs 500 nM 24 hours To study the effect of Syk inhibitor R788 on BMDMs, results showed that R788 downregulated the expression of immunosuppressive genes. PMC10416758
Healthy donor washed human platelets 10 µM 30 minutes R406 at 10 μM concentration reduced platelet adhesion on atherosclerotic plaque under static conditions but did not affect the platelet surface area. PMC9266367
THP-1 cells 10-20 μM 4 hours To evaluate the inhibitory effect of Fostamatinib on TBK1 phosphorylation. The results showed that Fostamatinib significantly inhibited the phosphorylation levels of TBK1 and IRF3. PMC10916235
Peritoneal macrophages 1 μM 6 h Inhibited LPS-induced mRNA transcription of TNF-α, IL-6, CCL2, CCL3, and CXCL10 PMC11606345
Neutrophils 1 μM 8 hours To evaluate the effect of R406 on LPS-induced NETosis in neutrophils, results showed that R406 effectively inhibited NETosis PMC11387147
NSC-34 cells 10 μM To evaluate the inhibitory effect of Fostamatinib on the cGAS/STING signaling pathway induced by ALS-related toxic proteins. The results showed that Fostamatinib significantly inhibited the phosphorylation of TBK1 and IRF3. PMC10916235

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Rats Conscious and anaesthetized rats Oral 10, 30, 100 mg/kg Single dose, up to 24 hours Fostamatinib dose-dependently increased blood pressure, and the time course of the BP effect correlated closely with the plasma concentrations of R406 PMC3997272
Mice Ferric chloride-induced carotid artery thrombosis model Oral 80 mg/kg Single dose Fostamatinib did not significantly affect arterial thrombus formation in mice. PMC9266367
C57BL/6 mice LPS-induced SIRS model Oral 7.5, 15, 30 mg/kg Once daily for 3 days Reduced LPS-induced inflammatory factor levels and inhibited excessive consumption of neutrophils in bone marrow PMC11606345
C57/B6 mice Pancreatic cancer model Intraperitoneal injection 50 mg/kg Five times per week, until tumor harvest To study the effect of R788 alone or in combination with Gem on pancreatic cancer tumor growth and metastasis, results showed that R788 significantly reduced tumor size and metastatic nodules. PMC10416758

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT00798096 T Cell Lymphoma PHASE2 COMPLETED 2025-04-10 Research Site, San Francisco, ... More >>California, 94143, United States|Research Site, Stanford, California, 94305, United States|Research Site, Atlanta, Georgia, 30322, United States|Research Site, Boston, Massachusetts, 02115, United States|Research Site, Rochester, Minnesota, 55905, United States|Research Site, Omaha, Nebraska, 68198, United States|Research Site, New York, New York, 10021, United States|Research Site, Houston, Texas, 77030, United States|Research Site, Vancouver, British Columbia, V5Z 4E6, Canada|Research Site, Toronto, Ontario, M5G 2M9, Canada Less <<
NCT02077192 Immune Thrombocytopenic Purpur... More >>a Less << PHASE3 COMPLETED 2020-06-02 Arizona Oncology Associates, T... More >>ucson, Arizona, 85710, United States|Bleeding & Clotting Disorders Institute, Peoria, Illinois, 61615, United States|Horizon Oncology Research, Inc, Lafayette, Indiana, 47905, United States|Center for Cancer and Blood Disorders, Bethesda, Maryland, 20817, United States|Weill Cornell Medical College/New York Presbyterian Hospital, New York, New York, 10065, United States|Weill Cornell Medicine, New York, New York, 10065, United States|East Carolina University, Brody School of Medicine, Greenville, North Carolina, 27834, United States|W.G. "Bill" Hefner VA Medical Center, Salisbury, North Carolina, 28144, United States|Signal Point Clinical Research Center LLC, Middletown, Ohio, 45042, United States|Concord Repatriation General Hospital, Concord, New South Wales, 2139, Australia|Liverpool Hospital, Liverpool, New South Wales, 2170, Australia|Prince of Wales Hospital, Randwick, New South Wales, 2031, Australia|Westmead Hospital, Westmead, New South Wales, 2145, Australia|Launceston General Hospital, Launceston, Tasmania, 7250, Australia|The Alfred, Melbourne, Victoria, 3004, Australia|Perth Blood Institute, Nedlands, Western Australia, 6009, Australia|Hanusch-Krankenhaus Wiener Gebietskrankenkasse, Vienna, 1140, Austria|Specialized Hospital for Active Treatment of Hematology Diseases, EAD, Sofia, Department of Chemotherapy, Hemotherapy and Blood Inherited Diseases to Clinic of Clinical Hematology;, Sofia, BG, 1756, Bulgaria|UMHAT Dr. Georgi Stranski, EAD, Pleven, Clinic of Hematology, Pleven, 5800, Bulgaria|UMHAT Aleksandrovska, EAD, Sofia, 1431, Bulgaria|MHAT Hristo Botev, AD, Vratsa, First Internal Department, Vratsa, 3000, Bulgaria|Hamilton Health Sciences Corporation, Hamilton, Ontario, L8N 3Z5, Canada|St. Michael's Hospital, Toronto, Ontario, M5B1W8, Canada|Fakultni nemocnice Brno, Brno, 625 00, Czechia|Fakultni nemocnice Ostrava, Ostrava-Poruba, 708 52, Czechia|Herlev Hospital, Herlev, DK, 2730, Denmark|Pecsi Tudomanyegyetem Klinikai Kozpont, I. sz. Belgyogyaszati Klinika, Pecs, H-7624, Hungary|Istituto di Ematologia "Lorenzo e Ariosto Seràgnoli", Bologna, BO, 40138, Italy|Azienda Ospedaliero-Universitaria "Santa Maria della Misericordia" - Clinica Ematologica, Udine, 33100, Italy|HAGA ziekenhuis, Den Haag, NL, 2545 CH, Netherlands|Haukeland universitetssykehus, Helse Bergen HF, Bergen, 5021, Norway|Sykehuset ?stfold Kalnes, Gr?lum, 1714, Norway|Samodzielny Publiczny Szpital Kliniczny Nr 1 we Wrocrlaw, Wroclaw, Dolnoslaski, 50-367, Poland|Wojewodzki Szpital Specjalistyczny im. J. Korczaka, Slupsk, PO, 76-200, Poland|Lkinika Hematologii I Transplantologii Uniwersyteckie Centrum Kliniczne, Gdansk, 80-952, Poland|SPZOZ Szpital Uniwersytecki w Krakowie Pracownia Separacji Krwinek i Bank Komórek Krwiotwórczych Klinika Hematologii, Kraków, 31-501, Poland|Wojewódzki Szpital Specjalistyczny im. M. Kopernika w ?odzi, Lodz, 93-510, Poland|Specjalistyczny Gabinet Lekarski, Lublin, 20-601, Poland|Szpital Wojewodzki w Opolu, Opole, 45-061, Poland|Instytut Hematologii I Transfuzjologii, Warszawa, 02-776, Poland|Spitalul Clinic Colentina, Hematologie, Bucuresti, 020125, Romania|Hospital Universitari Vall d'Hebron, Barcelona, 08035, Spain|Hospital Universitario La Paz, Madrid, 28046, Spain|Hospital Universitari i Politécnic La Fe de Valencia, Valencia, 46026, Spain|Colchester General Hospital, Colchester, Essex, CO4 5JL, United Kingdom|Royal Victoria Infirmary, Newcastle-upon-Tyne, UK, NE1 4LP, United Kingdom|Kent & Canterbury Hospital, Canterbury, CT1 3NG, United Kingdom|James Paget University Hospital, Great Yarmouth, NR31 6LA, United Kingdom|St. James's Hospital, Leeds, LS9 7TF, United Kingdom|Leicester Royal Infirmary, Leicester, LE1 5WW, United Kingdom|Royal Liverpool University Hospital, Liverpool, L78XP, United Kingdom|Imperial College Healthcare NHS Trust, London, W12 0HS, United Kingdom|University College Hospital, London, WC1E 6AG, United Kingdom|Cancer and Haematology Centre, Oxford, OX3 7LE, United Kingdom|University Hospital of North Midlands NHS Trust, Royal Stoke University Hospital, Stoke-on-Trent, ST4 6QG, United Kingdom Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.60mL

0.32mL

0.16mL

8.01mL

1.60mL

0.80mL

16.01mL

3.20mL

1.60mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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