Pharmacology and Experimental Therapeutics Research Group, School of Pharmacy and Medical Sciences, University of Bradford, Bradford BD7 1DP, UK.
Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK.
Trends Pharmacol Sci. 2019 May;40(5):298-308. doi: 10.1016/j.tips.2019.03.001. Epub 2019 Apr 2.
Defective regulation of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signalling pathway in cancers, haematological diseases, and chronic inflammatory conditions highlights its clinical significance. While several biologic and small molecule therapeutics targeting this pathway have been developed, these have several limitations. Therefore, there is a need to identify new targets for intervention. Suppressor of cytokine signalling (SOCS) proteins are a family of inducible inhibitors of cytokine receptors that activate the JAK-STAT pathway. Here we propose that newly identified mechanisms controlling SOCS function could be exploited to develop molecularly targeted drugs with unique modes of action to inhibit JAK-STAT signalling in disease.
在癌症、血液疾病和慢性炎症性疾病中，Janus 激酶-信号转导子和转录激活子（JAK-STAT）信号通路的调节失常凸显了其临床意义。虽然已经开发出了几种针对该通路的生物制剂和小分子治疗药物，但这些药物存在多种局限性。因此，需要确定新的干预靶点。细胞因子信号转导抑制物（SOCS）蛋白是一类可诱导的细胞因子受体抑制剂，可激活 JAK-STAT 通路。在这里，我们提出，新发现的控制 SOCS 功能的机制可以被利用来开发具有独特作用模式的分子靶向药物，以抑制疾病中的 JAK-STAT 信号。
