Description
Cell permeable, specific inhibitor of p38 (SAPK2a). Inhibits p38 MAPK stimulation of MAPKAPK2 (IC50=70nM). Can inhibit the key cell cycle event of retinoblastoma protein phosphorylation in interleukin-2-stimulated T cells. Studies on the proximal regulator of this event, the PI(3)K (phosphoinositide 3-kinase)/Akt (protein kinase B; PKB) pathway, showed that SB203580 blocks the phosphorylation and activation of Akt by inhibiting the Akt kinase, phosphoinositide-dependent protein kinase 1 (PDK1). The concentrations of SB203580 required to block Akt phosphorylation (IC50= 3-5µM) are only approximately 10-fold higher than those required to inhibit p38 MAP kinase (IC50=0.3-0.5µM). These data define a new activity for this drug and suggest that extreme caution should be used when interpreting data when SB203580 has been used at concentrations above 1-2µM. Non-specific effects include inhibition of COX-1 and -2. Enhances clonal growth of skin epithelial progenitor cells and stimulates neural stem cell proliferation