Progress with FAK inhibitors in the patent literature (2020-present)

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that transduces signals from integrins, receptor tyrosine kinases, and growth factors to orchestrate cell adhesion, migration, and survival. Aberrant FAK hyperactivation promotes tumor proliferation, invasion, anti-apoptosis, and chemoresistance. Consequently, the recent U.S. FDA approval of the FAK inhibitor defactinib combined with avutometinib for recurrent KRAS-mutant low‑grade serous ovarian cancer (LGSOC) validates FAK as a clinically actionable anticancer target.

This review discusses recent advances in FAK inhibitor development, focusing on small-molecule patents published from January 2020 to August 2026. A systematic search of SciFinder and WIPO databases was conducted for this period. It categorizes these novel inhibitors into several classes and summarizes their structural features, biological activities, design strategies, and structure-activity relationships (SAR).

Recent advances in FAK drug discovery have driven a transition from conventional kinase inhibition toward broader FAK pathway modulation, including improved inhibitors, dual-target strategies, and targeted protein degradation. The clinical success of defactinib-based combination therapy validates the therapeutic potential of FAK targeting, while emerging approaches offer opportunities to overcome resistance. Future progress will depend on biomarker-guided patient selection, rational combination regimens, and exploration of non-catalytic FAK functions to achieve more effective and durable therapies.