MK2抑制剂噻吩类关键中间体的合成与表征
摘 要
p38 / MK2途径调节多种生物学功能，因此已被最广泛地用作抑制慢性炎性疾病的治疗靶标。迄今为止，已经发现了几种在临床前模型中具有有效抗炎作用的p38抑制剂，但由于严重的全身毒性问题，大多数在临床上都失败了。MK2是p38下游的丝氨酸-苏氨酸激酶，在应激和炎症刺激下通过p38的磷酸化直接激活。已经显示出MK2是调节促炎细胞因子的生物合成中的直接和必不可少的成分。MK2信号的破坏导致几种促炎性细胞因子产生的水平显着降低。基于以上原因，假定该方法与毒性较小的p38抑制剂具有相似的功效，则已将MK2鉴定为替代分子靶标，以阻断该途径。
关键词：MK2；丝裂原激活的蛋白激酶；激活的蛋白激酶2；p38MAPK途径信号；传导途径炎症
Synthesis and characterization of MK2 inhibitor thiophene key intermediates
ABSTRACT
The p38/MK2 pathway regulates a wide range of biological functions, and thus has most been explored as a therapeutic target for inhibition of severe and chronic inflammatory diseases. Till date, several p38 inhibitors with potent anti-inflammatory effects inpre-clinical models have been discovered, but most of them have failed in clinics due to serious systemic toxicity issues.
MK2 is a serine-threonine kinase downstream to p38 and is activated directly through phosphorylation of p38 under stressand inflammatory stimulus. MK2 has been shown to be a direct and essential component in regulating the biosynthesis of pro-inflammatory cytokines. Disruption of MK2 signaling leads to a significant reduction in the level of several pro-inflammatory cytokine production. For these reasons, MK2 has been identified as an alternate molecular target in order to block the pathway with an assumption that this approach would show similar efficacy as that of p38 inhibitors with lesser toxicity concerns.
Key words:MK2；Mitogen-activated protein kinase-activated；protein kinase-2；
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