A cell-permeable benzoylthiourea compound that is shown to compete against PIP3 for binding PH domains of Akt1 (IC50 >31uM), ARNO, GRP1, and P1. Effectively blocks PIP3-dependent cellular PI3K-PDK1-Akt signaling pathway activation in U87MG (25 to 100uM for 3d) and PDGF-induced Akt and GRP membrane translocation in serum-starved SUM159 cells (1h 100uM pretreatment), while being inactive against PDGF-induced Btk translocation or PMA-induced PLC-delta and TAPP1/2 translocations. Although DM-PIT-1 can be administered as a DMSO stock for effective culture treatments, incorporating DM-PIT-1 into PEG-PE mixed micelles enhances its solubility (up to 1mM) and i.v. dosing limit for more effective in vivo administrations (5% vs. 41% of control 4T1 tumor size in mice via 1mg/kg micelles-formulated or 0.4mg/kg free drug daily i.v., respectively).
Storage and Stability:Lyophilized powder may be stored at -20°C. Stable for 12 months at -20°C. Reconstitute with sterile ddH2O. Aliquot to avoid repeated freezing and thawing. Store at -20°C. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap. Further dilutions can be made in assay buffer.
