Tosposertib (TU2218) is a small-molecule inhibitor that inhibits dual ALK5/VEGFR2 with IC50 of 1.2 nM and 4.5 nM respectively.
TU2218 shows an IC50 of 101 nM in the SMAD2 phosphorylation assay using human whole blood and an IC50 of 52.5 nM in the VEGFR2 phosphorylation assay in human umbilical vein endothelial cells (HUVECs).
TU2218 inhibits immunosuppression induced by TGFβ or coculture with cancer cells or deficient costimulatory signal.
TU2218 blocks suppressive activity of regulatory T cell for proliferation of TCR-elicited effector T lymphocytes.
TU2218 normalizes the endothelial cell inactivation through inhibiting VEGF-VEGFR2 axis.
TU2218 induces antitumor activity in combination with anti-PD1 in B16F10 syngeneic model.
