Design and synthesis of an erdafitinib-based selective FGFR2 degrader

• Yumeng Jin,
• Shidong Wang,
• Sihan Pan,
• Shuqi Huang,
• Weichen Zhou,
• Xiaohao Huang,
• Lei Zheng and
• Lingfeng Chen

Beilstein J. Org. Chem. 2026, 22, 583–591, doi:10.3762/bjoc.22.44

• -selective degrader, and for the first time confirmed its ability to degrade the membrane-bound form of FGFR2. This work provides an innovative targeted protein degradation strategy for the treatment of FGFR2-driven tumors and holds significant potential for clinical application. Keywords: CRBN; erdafitinib

• ; FGFR2; selective degrader; Introduction Fibroblast growth factor receptors (FGFR) are a family of single-pass transmembrane receptor tyrosine kinases (RTKs) localized on the cell surface that bind to fibroblast growth factors [1][2][3]. Dimerization and autophosphorylation of FGFRs are induced by their

• screened, leading to the identification of LC-JD-6, a potent and FGFR2-selective degrader. This study establishes a fundamental framework for the rational design of therapeutic modalities targeting FGFR2 degradation, offering novel insights into protein homeostasis-based cancer intervention. Results and