SB 203580 is a pyridinyl imidazole which suppresses the p38 mediated activation of MAPKAP kinase-2 (MAPKAP K2 or MK2), yet does not disrupt JNK activity. Mitogen-activated protein kinases (MAPK) are a group of serine and threonine-specific kinases sensitive to cellular stress, heat shock and proinflammatory cytokines. p38 MAPK is critical for normal immune and inflammatory responses as it regulates the expression of many cytokines, transcription factors, and cell surface receptors. SB 203580 inhibits the phosphorylation of heat shock protein 27 (HSP 27). SB 203580 has been shown to induce the activation of Raf-1. SB 203580 has also been shown to prevent the activation of PKB/Akt by inhibiting phosphoinositide-dependent protein kinase 1 (PDK1). SB 203580 is a useful tool to assess the physiological roles of p38, and for deriving and maintaining embryonic stem cells.