SB 203580 is a p38 MAPK inhibitor with IC50 of 0.3-0.5 μM, 10-fold less sensitive to SAPK3(106T) and SAPK4(106T) and blocks PKB phosphorylation with IC50 of 3-5 μM.

Mitogen-activated protein kinases (MAPK) mediate signal transduction from cell surface receptors to the nucleus and are classified into various subtypes. p38 MAPK is activated by environmental stresses and inflammatory cytokines and is critical for normal immune and inflammatory responses as it regulates the expression of many cytokines, transcription factors, and cell surface receptors.SB 203580 is a pyridinyl imidazole inhibitor of p38 MAPK that specifically blocks its kinase activity. SB 203580 does not however, disrupt JNK activity, which is activated by similar stressors to those which activate p38 MAPK.p38 MAPK activity in heat-shocked HeLa cells and osmotically stressed PC12 cells is inhibited by SB 203580 with an IC50 value of 0.6 µM.SB 203580 also prevents the activation of PKB/Akt by inhibiting phosphoinositide-dependent protein kinase 1 (PDK1) at IC50 values of 3-5 µM.