R935788 (Fostamatinib disodium, R788)

R935788 (Fostamatinib disodium, R788) is a selective Syk inhibitor with an IC50 of 41 nM.R935788 (Fostamatinib disodium) 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 FcγR-mediated events,R935788 (Fostamatinib disodium, R788) also blocked BCR-mediated Ag presentation, thus broadly interrupting the humoral contributions to T cell-driven autoimmunity. Indeed, oral administration of R935788 (Fostamatinib disodium, R788) 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, R935788 (Fostamatinib disodium, R788) reduced total B cell numbers and total Ig concentrations. Interestingly, R935788 (Fostamatinib disodium, R788) increased the number of IL-10–producing 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. ^[1][2][3][4]

• [1] J Clin Pharmacol. 2011 Jan 5.;
• [2] Expert Opin Investig Drugs. ;
• [3] Blood. 2010 Dec 2.;116(23):4894-905.