CS-1273

IC50: 8 μM ( ¹²⁵ I-VEGF-A binding to PAE/NRP1); 3 μM (bt-VEGF-A binding to purified NRP1 b1 domain).

EG00229 (Compound 2; 0-100 μM; 48 hours; A549 cells) treatment causes a significant reduction in cell viability over a 48 hours incubation.
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.
EG00229 (Compound 2) selectively inhibits radiolabeled ¹²⁵ I-VEGF-A binding to porcine aortic endothelial (PAE)/NRP1, but not VEGFR2-expressing cells, with an IC ₅₀ 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 IC ₅₀ of 23 μM.

EG00229 (0-10 mg/kg; intraperitoneal injection; three times per week; for 4 weeks; NSG mice) treatment substantially reduces tumor growth and visible vascularization.