Small molecule drug discovery targeting the JAK-STAT pathway
- Journal Title
- Pharmacological Research
- 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.
- Publisher
- Elsevier
- Keywords
- JAK inhibitors; JAK-STAT pathway; autoimmune diseases; drug discovery; kinase
- Research Division(s)
- Structural Biology
- PubMed ID
- 38777110
- Publisher's Version
- https://doi.org/10.1016/j.phrs.2024.107217
- Open Access at Publisher's Site
https://doi.org/10.1016/j.phrs.2024.107217- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2024-06-24 11:25:21
Last Modified: 2024-06-28 03:12:16