VEGFR-2-IN-39 (PROTAC-5), a PROTAC that targets VEGFR-2 with an IC 50 of 208.6 nM, demonstrates low toxicity. It effectively inhibits the proliferation of EA.hy926, a type of HUVEC, in a concentration-dependent manner, achieving an IC 50 value of 38.65 µM [1].

VEGFR-2-IN-39 effectively reduces VEGFR-2 protein levels in a dose-dependent manner ([1], 0-60 μM; 0-72 h). At concentrations ranging from 10-40 μM over 72 hours, the compound prolongs the S phase and reduces the proportion of cells in the G1 phase in HUVEC cell cycles ([1]). Additionally, VEGFR-2-IN-39 induces apoptosis in HUVEC cells, also in a dose-dependent fashion ([1], 0.1-40 μM; 72 h). Western Blot analysis reveals a rapid degradation of VEGFR-2, with levels decreasing by 60% at 40 μM within 24 hours, and almost complete degradation by 48 hours ([1]). Cell cycle analysis shows a significant increase in the proportion of cells in the S phase, leading to stalled or delayed cell cycle progression, while simultaneously significantly reducing the number of cells in the G1 phase ([1]). Apoptosis analysis indicates a significant increase in the proportion of late apoptotic cells, scaling with the dose; control group (untreated) accounts for 5.34%, 10 μM for 6.94%, 20 μM for 8.32%, 30 μM for 15.6%, and 40 μM for 48.7% ([1]).