IN10028，为治疗实体瘤而发现的新一代FAK抑制剂

The development of small-molecule inhibitors targeting Focal Adhesion Kinase (FAK) has been ongoing for several decades. In May 2025, the FDA approved a combination therapy involving FAK and MEK/RAF inhibitors for the treatment of low-grade serous ovarian cancer, marking a significant advancement in FAK-targeted therapies. In this study, we present IN10028, a second-generation FAK inhibitor that demonstrates enhanced efficacy in combination therapies and favorable safety profiles. IN10028 effectively targets both FAK1 and FAK2, exhibiting IC50 values of 0.2 nM and 60.1 nM, respectively, and significantly inhibits FAK-related signaling pathways. Compared to IN10018, a first-generation FAK inhibitor, IN10028 shows superior cancer cell cytotoxicity. Notably, IN10028 also demonstrates stronger target engagement than several first-generation FAK inhibitors. Through experiments conducted in animal models, IN10028 was evaluated in both monotherapy and combination therapy settings, consistently outperforming multiple first-generation FAK inhibitors in terms of tumor growth inhibition. Additionally, pharmacokinetic and toxicity studies necessary for Investigational New Drug (IND) filing have been completed, with the IND application anticipated in December 2025.