PROTAC FGFR2 degrader 1 (compound N5) is a potent PROTAC that efficiently targets FGFR2, boasting a DC 50 value of 6.46 nM and an FGFR2 IC 50 of 0.08 nM. This compound exhibits significant anti-proliferative effects and high selectivity. It induces G0/G1 arrest in the cell cycles of KATOIII and SNU16 and inhibits apoptosis by diminishing the activation of p-ERK and p-PLCγ, the downstream proteins of FGFR2. Additionally, PROTAC FGFR2 degrader 1 maintains over 50% inhibition of gastric cancer cells at a concentration of 0.17 nM and effectively suppresses the growth of SNU16 xenograft tumors in a mouse model.

PROTAC FGFR2 degrader 1 在不同浓度和时间条件下表现出显著的生物活性。在KATO III 和 SNU16细胞线中，其IC 50值均小于0.17 nM（0-1000 nM；72 h）。通过西方印迹法（WB）证实，该化合物（500 nM；12 h）能够在KATO III细胞中特异性地降解FGFR2，此过程依赖于泛素-蛋白酶体系统（UPS）。此外，该化合物在（500、1000 nM；24 h）处理下可引起KATO III 和 SNU16 细胞在 G0/G1期的细胞周期阻滞。

PROTAC FGFR2 degrader 1（10 mg/kg, 20 mg/kg；腹腔注射）在SNU16小鼠皮下异种移植模型中有效抑制了胃癌细胞的生长，并显著减少了肿瘤的重量。