Small-Molecule Kinase Inhibitors Approved by the U.S. FDA in 2025: A Review

In 2025, the U. S. Food and Drug Administration (FDA) approved a total of 11 small-molecule kinase inhibitors (9 as monotherapies and 2 as components of a combination regimen), setting a new record for the highest annual approval count of this drug class. Their clinical indications and target profiles show an increasingly diversified trend.Among them, five agents were approved for non-oncology indications: the Bruton's tyrosine kinase (BTK) inhibitor rilzabrutinib for chronic immune thrombocytopenia; the BTK inhibitor remibrutinib for chronic spontaneous urticaria; the Janus kinase (JAK) inhibitor delgocitinib for chronic hand eczema; the colony-stimulating factor 1 receptor (CSF1R) inhibitor vimseltinib for tenosynovial giant cell tumor; and the mitogen-activated protein kinase kinase (MEK) inhibitor mirdametinib for neurofibromatosis type 1.Additionally, four agents were approved for non-small cell lung cancer, including the human epidermal growth factor receptor 2 (HER2) inhibitors sevabertinib and zongertinib, the epidermal growth factor receptor (EGFR) inhibitor sunvozertinib, and the ROS proto-oncogene 1 (ROS1) inhibitor taletrectinib.The remaining two agents were approved as a combination regimen: the MEK inhibitor avutometinib plus the focal adhesion kinase (FAK) inhibitor defactinib, for low-grade serous ovarian cancer. This article systematically reviews the 11 approved small-molecule kinase inhibitors from the perspectives of research background, molecular design strategies, clinical efficacy and safety, which may serve as a reference for subsequent drug R&D in this field.