EG00229 is a neuropilin 1 (NRP1) receptor antagonist. EG00229 selectively inhibits VEGF-A binding to NRP1 b1 domain with an IC₅₀ of 3 μM, but has no effect on VEGFA binding to VEGFR-1 and VEGFR-2^[1]. IC50 & Target: IC50: 8 μM (¹²⁵I-VEGF-A binding to PAE/NRP1); 3 μM (bt-VEGF-A binding to purified NRP1 b1 domain)^[1]. In Vitro: EG00229 (Compound 2; 0-100 μM; 48 hours; A549 cells) treatment causes a significant reduction in cell viability over a 48 hours incubation^[1].
EG00229 (Compound 2) 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^[1].
EG00229 (Compound 2) 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^[1]. In Vivo: EG00229 (0-10 mg/kg; intraperitoneal injection; three times per week; for 4 weeks; NSG mice) treatment substantially reduces tumor growth and visible vascularization^[2].