SB 203580 (hydrochloride)

869185-85-3

C21H17ClFN3OS

H2O : 8.43 mg/mL (20.37 mM; Need ultrasonic and warming); DMSO : 100 mg/mL (241.60 mM; Need ultrasonic)

MAPK/ERK Pathway; Autophagy; Autophagy

SB 203580 hydrochloride (RWJ 64809 hydrochloride) is a widely used p38 MAPK inhibitor with an IC₅₀ of 0.3-0.5 uM. SB 203580 hydrochloride shows more than 100-fold selectivity over Akt (PKB), LCK, and GSK-3beta. IC50 & Target: IC50: 0.3-0.5 uM (p38 MAPK)^[1] In Vitro: SB 203580 inhibits IL-2-driven T cell proliferation with an IC₅₀ of 3-5 uM, SB 203580 is able to inhibit the activity of PDK1 in a dose-dependent manner with an IC₅₀ in the 3-10 uM range^[1].
SB 203580 at a concentration of 1?uM is sufficient for inhibiting p38 kinase activity in TF-1 cells. SB 203580 at 5 and 10?uM enhances NF-kappaB-mediated gene transcription independently of phosphorylation on the transactivation domains of the p65 subunit. SB203580-mediated increase in NF-kappaB transcriptional activity is associated with enhanced phosphorylation of ERK1/2 and c-Jun N-terminal kinase (JNK), but not p38 kinase^[2].
SB203580 treatment does not decrease the phosphorylation of p38 MAPK, but it significantly reduces the phosphorylation of MAPKAPK2, HSP27, and ATF2^[4]. In Vivo: All animals challenged with NS (noninfected controls) and treated with either SB203580 or placebo survive. Compared with placebo, pretreatment with the highest dose of SB203580 (100 mg/kg) 1 hour before E. coli increases the hazards ratio of death. With E. coli, compared with placebo, at 48 hours, but not 24 hours, low and high dose SB203580 decrease phosphorylated p38 MAPK and the ratio of phosphorylated to total p38. High dose SB203580 decreases lung neutrophils on histology at 24 hours in a trend approaching significance (p = 0.09) and increases them significantly at 48 hours (p = 0.01) in patterns different over time^[3]. SB 203580 is evaluated in several models of cytokine inhibition and inflammatory disease. It is demonstrated clearly to be a potent inhibitor of inflammatory cytokine production in both mice and rats with IC₅₀ values of 15 to 25 mg/kg^[4].