Selective Targeting of STAT6: Recent Advances and Future Perspectives.

Signal transducer and activator of transcription 6 (STAT6) is a key transcription factor in cytokine signaling, serving as the central effector of the IL-4 and IL-13 pathways. STAT6 orchestrates a range of physiological and pathological processes, including immune homeostasis and tumor development, making it an attractive therapeutic target for Th2-driven diseases and certain cancers. While the development of STAT6-directed agents remains at an early stage, the rapid clinical progression of the highly selective degrader KT-621 has revitalized interest in this target. In this review, we systematically summarize recent advances in STAT6 inhibitors and degraders, with a focus on structural features, design strategies, and biological evaluation. We also highlight current challenges and future opportunities, aiming to provide useful guidance for the discovery and optimization of next-generation STAT6-directed therapeutics.