Armstrong Daniel, Hanafi Maha, Frett Brendan
Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Expert Opin Ther Pat. 2025 Aug;35(8):859-873. doi: 10.1080/13543776.2025.2519642. Epub 2025 Jun 17.
Rearranged during transfection (RET) is a receptor tyrosine kinase essential for cell signaling processes such as proliferation, differentiation, and migration. RET alterations, including point mutations and gene fusions, contribute to oncogenesis. Recent advances in precision oncology have led to the development of selective RET inhibitors with improved safety and efficacy profiles.
This review discusses recent innovations in RET inhibitor development, with a focus on small-molecule patents published from 2022 to 2024. A comprehensive literature search was conducted using SciFinder and PatentScope with the keywords 'RET' and 'RET inhibitor.' The review summarizes the structural classes, target profiles, and potential advantages of newly patented compounds, particularly those designed to overcome known resistance mechanisms.
While selective RET inhibitors such as selpercatinib have shown clinical success and expanded indications, their use is limited by adverse events and emerging resistance mechanisms. Next-generation RET inhibitors that address these limitations represent a critical frontier in drug development.
转染期间重排（RET）是一种受体酪氨酸激酶，对细胞增殖、分化和迁移等信号传导过程至关重要。RET改变，包括点突变和基因融合，会导致肿瘤发生。精准肿瘤学的最新进展促使开发出安全性和疗效更佳的选择性RET抑制剂。
本综述讨论了RET抑制剂开发的最新创新，重点关注2022年至2024年公布的小分子专利。使用SciFinder和PatentScope以“RET”和“RET抑制剂”为关键词进行了全面的文献检索。该综述总结了新获专利化合物的结构类别、靶点特征和潜在优势，特别是那些旨在克服已知耐药机制的化合物。
虽然塞普替尼等选择性RET抑制剂已取得临床成功并扩大了适应症，但其使用受到不良事件和新出现的耐药机制的限制。解决这些局限性的下一代RET抑制剂是药物开发的关键前沿领域。
