Targeting JAK2/STAT3 for the treatment of cancer: A review on recent advancements in molecular development using structural analysis and SAR investigations

Bioorg Chem. 2024 Feb:143:107095. doi: 10.1016/j.bioorg.2023.107095. Epub 2024 Jan 4.

Abstract

Cancer is indeed considered a hazardous and potentially life-threatening disorder. The JAK/STAT pathway is an important intracellular signaling cascade essential for many physiological functions, such as immune response, cell proliferation, and differentiation. Dysregulation of this pathway aids in the progression and development of cancer. The downstream JAK2/STAT3 signaling cascades are legitimate targets against which newer anticancer drugs can be developed to prevent and treat cancer. Understanding the mechanisms behind JAK2/STAT3 participation in cancer has paved the way for developing innovative targeted medicines with the potential to improve cancer treatment outcomes. This article provides information on the current scenario and recent advancements in the design and development of anticancer drugs targeting JAK2/STAT3, including structural analysis and SAR investigations of synthesized molecules. Numerous preclinical and clinical trials are ongoing on these inhibitors, which are highlighted to gain more insight into the broader development prospects of inhibitors of JAK2/STAT3.

Keywords: Anticancer agents; JAK2; JAK2/STAT3; SAR investigations; STAT3; Structural analysis.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Cell Line, Tumor
  • Janus Kinase 2 / antagonists & inhibitors
  • Janus Kinase Inhibitors* / chemistry
  • Janus Kinase Inhibitors* / pharmacology
  • Janus Kinases / antagonists & inhibitors
  • Neoplasms* / drug therapy
  • STAT Transcription Factors / antagonists & inhibitors
  • STAT3 Transcription Factor / antagonists & inhibitors
  • Signal Transduction
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Janus Kinase 2
  • Janus Kinase Inhibitors
  • Janus Kinases
  • STAT Transcription Factors
  • STAT3 Transcription Factor