Compounds > n4-(2-2-dimethyl-3-oxo-4h-pyrid(1-4)oxazin-6-yl)-5-fluoro-n2-(3-4-5-trimethoxyphenyl)-2-4-pyrimidinediamine

n4-(2-2-dimethyl-3-oxo-4h-pyrid(1-4)oxazin-6-yl)-5-fluoro-n2-(3-4-5-trimethoxyphenyl)-2-4-pyrimidinediamine and Glomerulonephritis

n4-(2-2-dimethyl-3-oxo-4h-pyrid(1-4)oxazin-6-yl)-5-fluoro-n2-(3-4-5-trimethoxyphenyl)-2-4-pyrimidinediamine has been researched along with Glomerulonephritis* in 2 studies

Other Studies

2 other study(ies) available for n4-(2-2-dimethyl-3-oxo-4h-pyrid(1-4)oxazin-6-yl)-5-fluoro-n2-(3-4-5-trimethoxyphenyl)-2-4-pyrimidinediamine and Glomerulonephritis

Article	Year
Comment on "Therapeutic targeting of Syk in autoimmune diabetes". Journal of immunology (Baltimore, Md. : 1950), 2011, Feb-15, Volume: 186, Issue:4 Topics: Aminopyridines; Autoimmune Diseases; Diabetes Mellitus, Type 2; Glomerulonephritis; Humans; Intracellular Signaling Peptides and Proteins; Morpholines; Oxazines; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Pyridines; Pyrimidines; Reperfusion Injury; Signal Transduction; Spleen; Syk Kinase	2011
A spleen tyrosine kinase inhibitor reduces the severity of established glomerulonephritis. Journal of the American Society of Nephrology : JASN, 2010, Volume: 21, Issue:2 Antibody-mediated glomerulonephritis, including that resulting from immune complexes, is an important cause of renal failure and is in need of more specific and effective treatment. Binding of antibody or immune complexes to Fc receptors activates intracellular signal transduction pathways, including spleen tyrosine kinase (Syk), leading to the production of inflammatory cytokines. We examined the effect of R788 (fostamatinib disodium), an oral prodrug of the selective Syk inhibitor R406, in nephrotoxic nephritis in Wistar-Kyoto rats. Treatment with R788 reduced proteinuria, tissue injury, glomerular macrophage and CD8+ cell numbers, and renal monocyte chemoattractant protein-1 (MCP-1) and IL-1beta, even when we started treatment after the onset of glomerulonephritis. When we administered R788 from days 4 to 10, glomerular crescents reduced by 100% (P < 0.01) compared with the vehicle group. When we administered R788 treatment from days 7 to 14, established glomerular crescents reversed (reduced by 21%, P < 0.001), and renal function was better than the vehicle group (P < 0.001). In vitro, R406 downregulated MCP-1 production from mesangial cells and macrophages stimulated with aggregated IgG. These results suggest that Syk is an important therapeutic target for the treatment of glomerulonephritis. Topics: Aminopyridines; Animals; Cells, Cultured; Chemokine CCL2; Disease Models, Animal; Glomerulonephritis; Interleukin-1beta; Intracellular Signaling Peptides and Proteins; Macrophages; Mesangial Cells; Morpholines; Oxazines; Protein-Tyrosine Kinases; Pyridines; Pyrimidines; Rats; Rats, Inbred WKY; Severity of Illness Index; Signal Transduction; Syk Kinase	2010

Article

Year

Comment on "Therapeutic targeting of Syk in autoimmune diabetes".

Journal of immunology (Baltimore, Md. : 1950), 2011, Feb-15, Volume: 186, Issue:4

Topics: Aminopyridines; Autoimmune Diseases; Diabetes Mellitus, Type 2; Glomerulonephritis; Humans; Intracellular Signaling Peptides and Proteins; Morpholines; Oxazines; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Pyridines; Pyrimidines; Reperfusion Injury; Signal Transduction; Spleen; Syk Kinase

2011

A spleen tyrosine kinase inhibitor reduces the severity of established glomerulonephritis.

Journal of the American Society of Nephrology : JASN, 2010, Volume: 21, Issue:2

Antibody-mediated glomerulonephritis, including that resulting from immune complexes, is an important cause of renal failure and is in need of more specific and effective treatment. Binding of antibody or immune complexes to Fc receptors activates intracellular signal transduction pathways, including spleen tyrosine kinase (Syk), leading to the production of inflammatory cytokines. We examined the effect of R788 (fostamatinib disodium), an oral prodrug of the selective Syk inhibitor R406, in nephrotoxic nephritis in Wistar-Kyoto rats. Treatment with R788 reduced proteinuria, tissue injury, glomerular macrophage and CD8+ cell numbers, and renal monocyte chemoattractant protein-1 (MCP-1) and IL-1beta, even when we started treatment after the onset of glomerulonephritis. When we administered R788 from days 4 to 10, glomerular crescents reduced by 100% (P < 0.01) compared with the vehicle group. When we administered R788 treatment from days 7 to 14, established glomerular crescents reversed (reduced by 21%, P < 0.001), and renal function was better than the vehicle group (P < 0.001). In vitro, R406 downregulated MCP-1 production from mesangial cells and macrophages stimulated with aggregated IgG. These results suggest that Syk is an important therapeutic target for the treatment of glomerulonephritis.

Topics: Aminopyridines; Animals; Cells, Cultured; Chemokine CCL2; Disease Models, Animal; Glomerulonephritis; Interleukin-1beta; Intracellular Signaling Peptides and Proteins; Macrophages; Mesangial Cells; Morpholines; Oxazines; Protein-Tyrosine Kinases; Pyridines; Pyrimidines; Rats; Rats, Inbred WKY; Severity of Illness Index; Signal Transduction; Syk Kinase

2010