Picropodophyllin

A potent and selective inhibitor of insulin-like growth factor 1 receptor (IGF-1R, IC₅₀=6 nM). It efficiently blocks IGF-1R activity, reduces pAKT and pERK1/2, induces apoptosis in IGF-1R-positive tumor cells and causes complete tumor regression in xenografted and allografted mice. Picropodophyllin downregulates IGF-1R by interfering with the action of β-arrestin 1/MDM2. It causes tumor regression and attenuates invasiveness of uveal melanoma cells. It displays beneficial effects on tumor growth, angiogenesis, bone disease and survival in a mouse multiple myeloma model. It attenuates intimal hyperplasia after vascular injury. Inhibition of IGF-1R is non-competitive with ATP.