Targeting the STAT3 pathway with STAT3 degraders.

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.