Lee J C, Laydon J T, McDonnell P C, Gallagher T F, Kumar S, Green D, McNulty D, Blumenthal M J, Heys J R, Landvatter S W, Strickler J E, McLaughlin M M, Siemens I R, Fisher S M, Livi G P, White J R, Adams J L, Young P R
Department of Cellular Biochemistry, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406.
Nature. 1994;372(6508):739-46. doi: 10.1038/372739a0.
Production of interleukin-1 and tumour necrosis factor from stimulated human monocytes is inhibited by a new series of pyridinyl-imidazole compounds. Using radiolabelled and radio-photoaffinity-labelled chemical probes, the target of these compounds was identified as a pair of closely related mitogen-activated protein kinase homologues, termed CSBPs. Binding of the pyridinyl-imidazole compounds inhibited CSBP kinase activity and could be directly correlated with their ability to inhibit cytokine production, suggesting that the CSBPs are critical for cytokine production.
一系列新的吡啶基咪唑化合物可抑制人单核细胞受刺激后产生白细胞介素-1和肿瘤坏死因子。利用放射性标记和放射光亲和标记的化学探针,确定这些化合物的作用靶点是一对密切相关的丝裂原活化蛋白激酶同系物,称为CSBPs。吡啶基咪唑化合物的结合抑制了CSBP激酶活性,并且与其抑制细胞因子产生的能力直接相关,这表明CSBPs对细胞因子的产生至关重要。