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R406, an Orally Available Spleen Tyrosine Kinase Inhibitor Blocks Fc Receptor Signaling and Reduces Immune Complex-Mediated Inflammation
- S. Braselmann, V. Taylor, +18 authors E. Masuda
- Biology, MedicineJournal of Pharmacology and Experimental…
- 1 December 2006
A first-inhuman study is reported showing that R406 is orally bioavailable, achieving exposures capable of inhibiting Syk-dependent IgE-mediated basophil activation and showing R406 potential for modulating Syk activity in human disease.
NFATx, a novel member of the nuclear factor of activated T cells family that is expressed predominantly in the thymus
The expression pattern of NFATx, together with its functional activity, strongly suggests thatNFATx plays a role in the regulation of gene expression in T cells and immature thymocytes.
Signalling into the T-cell nucleus: NFAT regulation.
Quantitative measurement of mast cell degranulation using a novel flow cytometric annexin-V binding assay.
The annexin-V binding assay represents a powerful new flow cytometric method to monitor mast cell degranulation for functional analysis and was blocked by phosphatidylserine containing liposomes, consistent with specific binding to this membrane lipid.
The granulocyte-macrophage colony-stimulating factor promoter cis-acting element CLE0 mediates induction signals in T cells and is recognized by factors related to AP1 and NFAT.
- E. Masuda, H. Tokumitsu, +4 authors N. Arai
- Biology, MedicineMolecular and cellular biology
- 1 December 1993
The presence of CLE0-like elements in the promoters of interleukin-3 (IL-3), IL-4, IL-5, GM-CSF, and NFAT sites in the IL-2 promoter suggests that the factors detected, or related factors that recognize these sites, may account for the coordinate induction of these genes during T-cell activation.
Inhibition of spleen tyrosine kinase prevents mast cell activation and airway hyperresponsiveness.
- S. Matsubara, Guiming Li, +8 authors E. Gelfand
- MedicineAmerican journal of respiratory and critical care…
A functional role for Syk is delineated in the development of mast cell- and IgE-mediated AHR and airway inflammation, and these results indicate that inhibition of Syk may be a target in the treatment of allergic asthma.
Syk activation in dendritic cells is essential for airway hyperresponsiveness and inflammation.
- S. Matsubara, T. Koya, +6 authors E. Gelfand
- Biology, MedicineAmerican journal of respiratory cell and…
- 1 April 2006
It is demonstrated that Syk inhibition prevents allergen-induced AHR and airway inflammation after systemic sensitization and challenge, at least in part through alteration of DC function.
A spleen tyrosine kinase inhibitor reduces the severity of established glomerulonephritis.
- Jennifer Smith, J. McDaid, +5 authors F. Tam
- MedicineJournal of the American Society of Nephrology…
- 1 February 2010
Results suggest that Syk is an important therapeutic target for the treatment of glomerulonephritis, and in vitro, R406 downregulated MCP-1 production from mesangial cells and macrophages stimulated with aggregated IgG.
A Novel E3 Ubiquitin Ligase TRAC-1 Positively Regulates T Cell Activation
- Haoran Zhao, Connie C Li, +13 authors E. Masuda
- Biology, MedicineThe Journal of Immunology
- 1 May 2005
The results of in vitro biochemical studies indicate that TRAC-1 can stimulate the formation of both K48- and K63-linked polyubiquitin chains and therefore could potentially activate both degradative and regulatory ubiquitin-dependent pathways.
Developmental toxicity associated with receptor tyrosine kinase Ret inhibition in reproductive toxicity testing.
- G. Clemens, R. Schroeder, +6 authors E. Grossbard
- Biology, MedicineBirth defects research. Part A, Clinical and…
- 1 February 2009
A dose-dependent increase in malformations, including renal and ureteric agenesis and a specific major vessel anomaly, retroesophageal right subclavian artery, was observed in both the rat and rabbit as R788 proved to be a potent inhibitor of Ret kinase.