Fostamatinib disodium (R788, R-935788) is a potent, ATP-competitive and selective Syk (Spleen tyrosine kinase) inhibitor with IC50 of 41 nM. It is an orally available disodium salt of the Syk kinase inhibitor fostamatinib with potential anti-inflammatory and immunomodulating activities. Syk kinase, widely expressed in hematopoietic cells, is a nonreceptor tyrosine kinase that is involved in coupling activated immunoreceptors to signal downstream events that mediate diverse cellular responses, including proliferation, differentiation, and phagocytosis. Fostamatinib disodium (R788) inhibits tumor growth in the Eμ- TCL1 transgenic mouse model of CLL by blocking antigen-dependent B-cell receptor signaling. It effectively inhibits BCR signaling in vivo, resulting in reduced proliferation and survival of the malignant B cells and significantly prolonged survival of the treated animals. The growth-inhibitory effect of Fostamatinib disodium occurs despite the relatively modest cytotoxic effect in vitro and is independent of basal Syk activity, suggesting that Fostamatinib disodium (R788) functions primarily by inhibiting antigen-dependent BCR signals. Importantly, the effect of Fostamatinib disodium was found to be selective for the malignant clones, as no disturbance in the production of normal B lymphocytes was observed.
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
Selective, novel spleen tyrosine kinase (Syk) inhibitors suppress chronic lymphocytic leukemia B-cell activation and migration.
Hoellenriegel et al. Leukemia. 2012 Jul;26(7):1576-83. PMID: 22362000.
Spleen tyrosine kinase (Syk) is a potent target for GvHD prevention at different cellular levels.
Leonhardt et al. Leukemia. 2012 Jul;26(7):1617-29. PMID: 22301676.
Syk inhibition with fostamatinib leads to transitional B lymphocyte depletion.
Barr et al. Clin Immunol. 2012 Mar;142(3):237-42. PMID: 22284392.
The oral spleen tyrosine kinase inhibitor fostamatinib attenuates inflammation and atherogenesis in low-density lipoprotein receptor-deficient mice.
Hilgendorf et al. Arterioscler Thromb Vasc Biol. 2011 Sep;31(9):1991-9. PMID: 21700926.
|Related Syk Products|
R112 is an ATP-competitive inhibitor of Syk kinase with an IC50 of 226 nM.
PRT-060318 (PRT318) is a novel selective inhibitor of the Syk tyrosine kinase, as an approach to HIT treatment.
BAY-61-3606 is a potent and selective inhibitor of Syk kinase (Ki = 7.5 nM).
Piceatannol, a natural stilbene, is a selective Syk inhibitor and ~10-fold selectivity versus Lyn.
GS-9973 is an orally bioavailable, selective Syk inhibitor with IC50 of 7.7 nM.
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