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Skeletal Phenotype Analysis of a Conditional Stat3 Deletion Mouse Model
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Targeting the STAT3 pathway with STAT3 degraders.

Zhijie Wang1, Xiaotong Liao2, Haiqi He2

  • 1Shenzhen Key Laboratory of Viral Oncology, Ministry of Science and Innovation, Shenzhen Hospital, Southern Medical University, Shenzhen 518100, China; Guangdong Provincial Key Laboratory of New Drug Screening, NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.

Trends in Pharmacological Sciences
|August 8, 2024
PubMed
Summary

Signal transducer and activator of transcription 3 (STAT3) degraders offer a promising therapeutic strategy for diseases like cancer. This review explores STAT3 degraders, including PROTACs and natural products, highlighting their mechanisms and potential for drug development.

Keywords:
PROTACsSTAT3degradersinhibitorssmall-molecule natural products

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Pharmacology

Background:

  • Signal transducer and activator of transcription 3 (STAT3) is a key therapeutic target for numerous diseases, particularly cancers.
  • STAT3 inhibitors face development challenges, necessitating alternative strategies.
  • STAT3 degraders have emerged as a promising approach to inhibit STAT3 function.

Purpose of the Study:

  • To review recent advancements in STAT3 degraders.
  • To focus on proteolysis targeting chimeras (PROTACs) and small-molecule natural products.
  • To discuss structures, mechanisms, biological activities, opportunities, and challenges of STAT3 degraders.

Main Methods:

  • Literature review of recent advancements in STAT3 degrader research.
  • Analysis of structural and mechanistic properties of STAT3 degraders.
  • Evaluation of biological activities and therapeutic potential.

Main Results:

  • STAT3 degraders, including PROTACs and natural products, demonstrate significant potential in blocking STAT3.
  • Recent research has elucidated diverse structures and mechanisms of action for these degraders.
  • Various STAT3 degraders have shown promising biological activities in preclinical studies.

Conclusions:

  • STAT3 degraders represent a viable and innovative strategy for targeting STAT3 in disease treatment.
  • Further research into the opportunities and challenges will facilitate the development of potent STAT3-targeting drugs.
  • This review provides insights into the discovery and development of novel STAT3 degrader-based therapeutics.