产品描述:
IPI-549 is an inhibitor of PI3Kγ (IC50s = 16, 3,200, 3,500, and >8,400 nM for PI3Kγ, PI3Kα, PI3Kβ, and PI3Kδ, respectively).{42626} It is greater than 100-fold selective for PI3Kγ over a panel of 468 mutant and nonmutant protein and lipid kinases, including Class II PI3K isoforms, and a panel of 80 G protein-coupled receptors, ion channels, and transporters at 10 µM. It inhibits phosphorylation of AKT S473 in SKOV3, 786-0, RAW 264.7, and RAJI cells and inhibits migration of bone marrow-derived macrophages (BMDMs) (IC50 = 85 nM). IPI-549 sensitizes doxorubicin-resistant SW620/Ad300 cells to P-glycoprotein (P-gp) substrates, such as paclitaxel (IC50s = 710 and 6.7 nM for paclitaxel alone and in combination with IPI-549, respectively), and increases the level of intracellular paclitaxel in SW620/Ad300 cells.{42627} It also enhances the tumor growth reduction of paclitaxel (Item No. 10461) in an SW620/Ad300 mouse xenograft model when administered at a dose of 3 mg/kg in combination with paclitaxel.