SB203580[4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1Himidazole][6]是一种特异性的吡啶咪唑类p38-MAPK (促分裂原活化蛋白激酶)信号通路抑制剂[1] [3]。SB203580与ATP竞争结合ATP结合口袋内部或附近的非保守区域，Ki值为21 nM [3]。在体外，SB203580也可以抑制c-Raf，IC50值为2 mM [4]。

P38 MAPK信号通路使细胞针对一系列外部信号做出相应的反应。在该途径中依次起作用的三个蛋白激酶的核心确保细胞内反应的多样性和特异性[5]。

用30 mM的SB203580处理显著减少L1210/VCR细胞对vincristine的耐受性，使得vincristine的LC50值从3.2036±0.521变为0.5576±0.082 mM。10 mM的SB203580处理轻微改变了耐药指数，使得SB203580在敏感的L1210细胞和耐受细胞中的LC50值分别为39.26±2.2 mM和52.06±7.6 mM [1]。

在体内，在永久性大脑中动脉闭塞之前24小时用SB203580单独给药废除了异氟醚（isoflurane）预处理诱导的神经保护作用。在异氟醚处理后，SB203580减少磷酸化的p38 MAPK。SB203580也可以抑制茴香霉素（anisomycin）预处理诱导的神经保护[6]。

参考文献：
[1].  Miroslav Baranclk, Vierka Bohacova, Janka Kvackajova, et al. SB203580, a specific inhibitor of p38-MAPK pathway, is a new reversal agent of P-glycoprotein-mediated multidrug resistance. European Journal of Pharmaceutical Sciences, 2001, 14: 29-36.
[2].  Shuqiu Zheng and Zhiyi Zuo. Isoflurane Preconditioning Induces Neuroprotection against Ischemia via Activation of P38 Mitogen-Activated Protein Kinases. Molecular Pharmacology, 2004, 65:1172-1180.
[3].  Peter R. Young, Megan M. McLaughlin, Sanjay Kumar, et al. Pyridinyl Imidazole Inhibitors of p38 Mitogen-activated Protein Kinase Bind in the ATP Site. The Journal of Biological Chemistry, 1997, 272(18): 12116-12121.
[4].  Clare A Hall-Jackson, Michel Goedert, Philip Hedge, et al. E?ect of SB 203580 on the activity of c-Raf in vitro and in vivo. Oncogene, 1999, 18: 2047-2054.
[5].  Ana Cuadrado and Angel R. Nebreda. Mechanisms and functions of p38 MAPK signalling. Biochem. J., 2010, 429: 403-417.
[6].  Shuqiu Zheng and Zhiyi Zuo. Isoflurane Preconditioning Induces Neuroprotection against Ischemia via Activation of P38 Mitogen-Activated Protein Kinases. Mol Pharmacol, 2004, 65: 1172-1180.