EG01377 dihydrochloride is a potent, bioavailable and selective inhibitor of neuropilin-1 (NRP1), with a Kd of 1.32 μM, and IC50s of 609 nM for both NRP1-a1 and NRP1-b1. EG01377 dihydrochloride has antiangiogenic, antimigratory, and antitumor effects[1].
EG01377 (3-30 μM; 30 minutes) inhibits vascular endothelial growth factor A (VEGF-A) stimulated tyrosine phosphorylation of VEGF-R2/KDR[1].EG01377 (30 μM) is able to significantly reduce HUVEC cell migration in response to VEGFA[1].EG01377 (30 μM; 5 days) can delay the VEGF-induced wound closure[1].EG01377 (30 μM) reduces network area, length, and branching points[1].EG01377 (30 μM; 7 days) reduces VEGF-induced angiogenesis[1].EG01377 (30 μM; 7 days) in combination with VEGFA reduces A375P (malignant melanoma) spheroid outgrowth[1].EG01377 (500 nM; 2 hours) blocks the production of transforming growth factor beta (TGFβ) by Nrp1+ regulatory T-cell SMAD3/AKT (Tregs) in the presence of tumor cell-derived factors[1]. Western Blot Analysis[1] Cell Line: Human umbilical vein endothelial cells (HUVECs)
EG01377 (2 mg/kg; i.v.) exhibits an encouraging half-life of 4.29 h, sufficient to sustain once per day dosing in mice[1]. Animal Model: 6-8 week-old BABL/c female mice[1]
[1]. Powell J, et al. Small Molecule Neuropilin-1 Antagonists Combine Antiangiogenic and Antitumor Activity with Immune Modulation through Reduction of Transforming Growth Factor Beta (TGFβ) Production in Regulatory T-Cells. J Med Chem. 2018 May 10;61(9):4135-4154.