Abstract：
The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway functions as a central hub for transmitting signals from more than 50 cytokines, playing a pivotal role in maintaining hematopoiesis, immune balance, and tissue homeostasis. Dysregulation of this pathway has been implicated in various diseases, including immunodeficiency, autoimmune conditions, hematological disorders, and certain cancers. Proteins within this pathway have emerged as effective therapeutic targets for managing these conditions, with various approaches developed to modulate key nodes in the signaling process, spanning from receptor engagement to transcription factor activation. Following the success of JAK inhibitors such as tofacitinib for RA treatment and ruxolitinib for managing primary myelofibrosis, the pharmaceutical industry has obtained approvals for over 10 small molecule drugs targeting the JAK-STAT pathway and many more are at various stages of clinical trials. In this review, we consolidate key strategies employed in drug discovery efforts targeting this pathway, with the aim of contributing to the collective understanding of small molecule interventions in the context of JAK-STAT signaling. We aspire that our endeavors will contribute to advancing the development of innovative and efficacious treatments for a range of diseases linked to this pathway dysregulation.
摘要：
Janus激酶-信号转导子和转录激活因子（JAK-STAT）通路是传递来自50多种细胞因子的信号的中心枢纽，在维持造血方面发挥着关键作用，免疫平衡，和组织稳态。这种途径的失调与各种疾病有关，包括免疫缺陷,自身免疫性疾病，血液病,某些癌症。该途径中的蛋白质已成为管理这些疾病的有效治疗靶标，随着开发出各种方法来调制信令过程中的关键节点，从受体接合到转录因子激活。在JAK抑制剂如托法替尼治疗RA和鲁索替尼治疗原发性骨髓纤维化的成功之后，制药行业已经获得了超过10种针对JAK-STAT途径的小分子药物的批准,还有更多的药物正处于临床试验的不同阶段.在这次审查中,我们整合了针对该途径的药物发现工作中采用的关键策略，目的是促进在JAK-STAT信号传导的背景下对小分子干预的集体理解。我们希望，我们的努力将有助于推进创新和有效的治疗方法的发展，以治疗与该途径失调有关的一系列疾病。
