2025年美国FDA批准的小分子激酶抑制剂综述

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

摘要

2025年，美国食品药品监督管理局（Food and Drug Administration, FDA）共批准了11种小分子激酶抑制剂（其中9种为单药获批，2种为联合疗法获批），创历年小分子激酶抑制剂单年获批数量新高，其临床应用和靶点也呈现出更加多元化的趋势。其中，5种药物获批用于非癌症疾病，具体包括：布鲁顿酪氨酸激酶（Bruton's tyrosine kinase, BTK）抑制剂rilzabrutinib，治疗慢性免疫性血小板减少症；BTK抑制剂remibrutinib治疗慢性自发性荨麻疹；Janus激酶（Janus kinase, JAK）抑制剂delgocitinib治疗慢性手部湿疹；集落刺激因子1受体（colony stimulating factor 1 receptor, CSF1R）抑制剂vimseltinib治疗腱鞘巨细胞瘤；丝裂原活化蛋白激酶激酶（mitogen-activated protein kinase kinase, MEK）抑制剂mirdametinib治疗神经纤维瘤病1型。此外，有4种药物获批用于治疗非小细胞肺癌，包括人表皮生长因子受体2（human epidermal growth factor receptor 2, HER2）抑制剂sevabertinib和zongertinib、表皮生长因子受体（epidermal growth factor receptor, EGFR）抑制剂sunvozertinib和ROS原癌基因1（ROS proto-oncogene 1, ROS1）抑制剂taletrectinib。MEK抑制剂avutometinib和黏着斑激酶（focal adhesion kinase, FAK）抑制剂defactinib联合疗法获批用于治疗低级别浆液性卵巢癌。从研发背景、设计思路、临床疗效及安全性等方面，对2025年FDA批准的11种小分子激酶抑制剂进行系统阐述，以期对该领域后续药物研发工作提供参考与借鉴。

Abstract

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.

关键词

小分子激酶抑制剂 / FDA批准 / 分子靶向治疗 / 药物设计 / 临床安全性

Key words

small-molecule kinase inhibitors / FDA-approved / molecular targeted therapy / drug design / clinical safety

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