R788(FosD) is a selective Syk inhibitor with an IC50 of 41 nM. R788(FosD) has shown clinical activity in heavily pre-treated NHL and CLL patients, exhibits inhibitory activity against SYK but also inhibits a broad spectrum of other kinase targets. In addition to blocking Fc¦ÃR-mediated events, R788 also blocked BCR-mediated Ag presentation, thus broadly interrupting the humoral contributions to T cell-driven autoimmunity. Indeed, oral administration of R788(FosD) significantly delayed spontaneous diabetes onset in NOD mice and successfully delayed progression of early-established diabetes even when treatment was initiated after the development of glucose intolerance. At the DC level, R788 treatment was associated with reduced insulin-specific CD8 priming and decreased DC numbers. At the B cell level, R788(FosD) reduced total B cell numbers and total Ig concentrations. Interestingly, R788(FosD) increased the number of IL-10¨Cproducing B cells, thus inducing a tolerogenic B cell population with immunomodulatory activity. Taken together, Syk in APCs is an attractive target in T cell-mediated autoimmune diseases such as type 1 diabetes.

June 21, 2017

prudect name : R788(FosD) is a selective Syk inhibitor with an IC50 of 41 nM. R788(FosD) has shown clinical activity in heavily pre-treated NHL and CLL patients, exhibits inhibitory activity against SYK but also inhibits a broad spectrum of other kinase targets. In addition to blocking Fc¦ÃR-mediated events, R788 also blocked BCR-mediated Ag presentation, thus broadly interrupting the humoral contributions to T cell-driven autoimmunity. Indeed, oral administration of R788(FosD) significantly delayed spontaneous diabetes onset in NOD mice and successfully delayed progression of early-established diabetes even when treatment was initiated after the development of glucose intolerance. At the DC level, R788 treatment was associated with reduced insulin-specific CD8 priming and decreased DC numbers. At the B cell level, R788(FosD) reduced total B cell numbers and total Ig concentrations. Interestingly, R788(FosD) increased the number of IL-10¨Cproducing B cells, thus inducing a tolerogenic B cell population with immunomodulatory activity. Taken together, Syk in APCs is an attractive target in T cell-mediated autoimmune diseases such as type 1 diabetes.
Fostamatinib disodium

Synonyms: R788CAS NO: 1025687-58-4Molecular Formula: C₂₃H₂₄FN₆O₉P.₂NaMolecular Weight: 624.42Purity: 98% minSolubility: In DMSOStorage: −20°C

AMG 337 References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/18514728