PI-103 (C007B-247913)

InformationPI-103 is a multi-targeted PI3K inhibitor forp110α/β/δ/γwithIC50of 2 nM/3 nM/3 nM/15 nM in cell-free assays, less potent to mTOR/DNA-PK withIC50of 30 nM/23 nM. PI-103 inducesapoptosisin murine T-cell Lymphoma.In vitroPI-103 potently inhibits both the rapamycin-sensitive (mTORC1) and rapamycin-insensitive (mTORC2) complexes of the protein kinase mTOR. PI-103 inhibits constitutive and growth factor-induced PI3K/Akt, as well as mTORC1 activation. In blast cells, PI-103 inhibits leukemic proliferation, the clonogenicity of leukemic progenitors and induces mitochondrial apoptosis, especially in the compartment containing leukemic stem cells. PI-103 inhibits p110α >200-fold more potently than p110β. PI-103 also potently blocks production of PI(3,4)P2 and PIP3 in adipocytes and PIP3 in myotubes. PI-103 inhibits phosphorylation of Akt with an IC95 100-fold lower than that for LY294002. Strikingly, PI-103 completely protects animals from insulin-stimulated decline in blood glucose. PI-103 has additive proapoptotic effects with etoposide in blast cells and in immature leukemic cells.In vivoWhen tumors reach 50-100 mm3, animals are randomized and treated with vehicle or PI-103. PI-103 exhibits significant activity, decreasing average tumor size by 4-fold after 18 days. Mice treated with PI-103 have no obvious signs of toxicity premorbidly (based on body weight, food and water intake, activity, and general exam) or at necropsy. Treated tumors display decreased levels of phosphorylated Akt and S6, consistent with blockade of p110α and mTOR. PI-103 treatment is cytostatic to glioma xenografts.Cell Datacell lines：H23, H460, A549, and H358 cellsConcentrations：0.5 μMIncubation Time：24 hoursPowder Purity:≥99%.

Specifications and Purity: 10mM in DMSO

Molecular Formula: C19H16N4O3

Molecular Weight: 348.36