EG00229 is a neuropilin 1 (NRP1) receptor antagonist that selectively inhibits the binding of VEGF-A to the NRP1 b1 domain, achieving this inhibition with an IC50 value of 3 μM. It does not affect the binding of VEGF-A to other receptors, such as VEGFR-1 and VEGFR-2.

Bt-VEGF-A binding to purified NRP1 b1 domain:3 μM , [125I]-VEGF-A binding to PAE/NRP1:8 μM

EG00229 selectively inhibits radiolabeled 125I-VEGF-A binding to porcine aortic endothelial (PAE)/NRP1, but not VEGFR2-expressing cells, with an IC50 of 8 μM. EG00229 also inhibits VEGF-A binding to lung carcinoma A549 and prostate carcinoma DU145 cells, which express NRP1, but not VEGFR1 and VEGFR2, with similar potency. Binding of VEGF-A to human umbilical vein endothelial cells (HUVECs), which express VEGFR2, VEGFR1, and NRP1, is also inhibited by EG00229 with an IC50 of 23 μM.EG00229 ( 0-100 μM; 48 hours; A549 cells) treatment causes a significant reduction in cell viability over a 48 hours incubation. EG00229 demonstrates inhibition of VEGF-A binding to NRP1 and attenuates VEGFR2 phosphorylation in endothelial cells. Inhibition of migration of endothelial cells is also observed in HUVECs.

EG00229 treatment substantially reduces tumor growth and visible vascularization.