PP121

PP121 is a dual inhibitor of receptor tyrosine kinases (RTKs) (IC50 < 0.02 μM for Abl, Src, VEGFR-2 and PDGFR) and PI 3-K family kinases (IC50 < 0.06 μM for p110α, DNA-PK and mTOR). PP121 is the first inhibitor active on both Tyrosine kinases and the phosphatidylinositol-3-OH kinase (PI(3)K) family. PP121 blocks the proliferation of tumor cells by direct inhibition of PI 3-K, mTOR, Src and the VEGF receptor. PP-121 induces a G0/G1 arrest in LN220, U87 and Seg1 cells. PP-121 directly inhibits Bcr-Abl induced tyrosine phosphorylation, resulting in drug-induced apoptosis in K562 cells and a combination of apoptosis and cell cycle arrest in Bcr-Abl expressing BaF3 cells. PP-121 also inhibits other PI3Ks including p110α and DNA-PK with IC50 of 52 nM and 60 nM, respectively.