proliferative proteins in HUVECs. Treatment of HUVECs with 500 nM of TGP-377 increased levels of excreted VEGFA in HUVEC media supernatants by 2-fold (Fig. ), with a similar effect observed by Western blot of intracellular VEGFA (Fig. ). Global proteomics analysis of the HUVEC proteome (>4000 unique proteins) revelated that only 160 proteins were affected by TGP-377 treatment (p <0.05; Fig. ). A bioinformatic STRING analysis was performed to study protein association networks that are affected by TGP-377. This showed that, as expected, cell proliferative pathways including FGFR, Hedgehog, MAP kinase, and ERK pathways were upregulated. Previous studies have shown that upregulation of VEGFA causes a reduction of Hedgehog interacting protein (HHIP) levels, part of a larger feedback loop for angiogenesis. As expected, levels of HHIP were significantly reduced upon TGP-377 treatment (p<0.01; Fig. ). Of interest, levels of Protein Phosphatase 2 Regulatory Subunit B'Alpha (PPP2R5A) were also significantly reduced upon treatment (p<0.05; Fig. ). PPP2R5A, which is part of a pathway that controls cell survival, has been previously shown to be downregulated upon upregulation of VEGFA. Other affected proteins that are known to be modulated specifically within the VEGFA-mediated pathways can be found in Table . Collectively, these studies show that TGP-377 exerts selective effects on the proteome and indeed broadly affects signaling via the VEGFA pathway.