FGFR4 Degrader

PROTAC FGFR4 degrader-1 is a selective FGFR4 PROTAC degrader with DC₅₀ = 0.84 μM. PROTAC FGFR4 degrader-1 is obtained by coupling the FGFR4 covalent inhibitor H3B-6527 (HY-100491) with a VHL E3 ubiquitin ligase ligand via an alkyl linker, and achieves FGFR4 degradation through the ubiquitin-proteasome system. PROTAC FGFR4 degrader-1 can induce apoptosis in hepatocellular carcinoma cells and inhibit FGFR4-driven proliferation of hepatocellular carcinoma cells. PROTAC FGFR4 degrader-1 can downregulate RNA polymerase and aminoacyl-tRNA biosynthesis while upregulating DNA replication. PROTAC FGFR4 degrader-1 can be used for research on hepatocellular carcinoma.

CYB-5067 is a FGFR molecular glue degrader with a DC₅₀ of 27 nM against FGFR2. CYB-5067 inhibits FGFR1, FGFR3, FGFR4 and downstream FGFR signaling pathways, induces antiproliferative activity in vitro, and exhibits sustained target protein inhibition in vivo without obvious hook effect. CYB-5067 shows significant tumor growth inhibitory activity in the ETV6-FGFR2 fusion Ba/F3 xenograft model. CYB-5067 can be used for the research of FGFR-driven cancers.