创新链/学科链/研发链/产业链

新药研发前沿动态 / 医药领域趋势进展

凋亡信号调节激酶1抑制剂的研究进展

Research Progress of Apoptosis Signal Regulating Kinase 1 Inhibitors

  • 摘要: 凋亡信号调节激酶1(ASK1)是细胞丝裂原活化蛋白激酶激酶激酶(MAP3K)家族成员之一,其调控的ASK1-c-Jun氨基末端激酶(JNK)-p38丝裂原活化蛋白激酶(p38)信号通路与多种疾病密切相关。在细胞应激的刺激下ASK1被激活,诱导其下游JNK和p38磷酸化,进而激活下游细胞因子,促进细胞增殖、分化、凋亡及炎症因子的产生,导致机体出现破坏性的炎症反应、细胞死亡与纤维化。目前,ASK1抑制剂已在如肾脏、肝脏、中枢神经系统和关节等疾病中表现出治疗潜力。综述ASK1抑制剂的研究进展及其在疾病治疗中的潜在应用,旨在为该类抑制剂的设计与开发提供参考。

     

    Abstract: Apoptosis signal-regulating kinase 1 (ASK1) is a member of the mitogen-activated protein kinase kinase kinase (MAP3K) family of cellular mitogen-activated protein kinases, and its regulated ASK1-JNK-p38 signaling pathway is closely related to various diseases. Under the stimulation of cellular stress, ASK1 will be activated and induce phosphorylation of its downstream c-Jun aminoterminal kinases (c-JNK) and p38 kinases, which will activate the downstream cytokines to promote cell proliferation, differentiation, apoptosis, and production of inflammatory factors, leading to destructive inflammation, cell death, and fibrosis in the organism. Currently, the therapeutic potential of ASK1 inhibitors has been observed in a variety of diseases of the kidney, liver, central nervous system and joints. This paper reviews the potential application of ASK1 inhibitors in the treatment of diseases and the research progress of ASK1 inhibitors, aiming to provide some guidance for the design and development of ASK1 inhibitors.

     

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