PF-06424439

PF-06424439 is a first orally bioavailable small-molecule inhibitor of DGAT2 with an IC50 of 14 nM.

PF-06424439 treatment reduces LD content and inhibites cell migration, without affecting cell proliferation.  PF-06424439 pre-treatment followed by radiation can enhance radiosensitivity of MCF7 cells.^{<a class="sref" href="#s_ref">[2]</a>}

MCF7 cells are seeded at 4.7 × 10³ cells/well in 96-well black polystyrene microplates and incubated overnight at 37 °C to allow for cell attachment. The next day, cells are treated with 1, 10, 50, 100, 200 μM of PF-06424439 for 24, 48, 72, and 96 h, and then used for Cell Viability Assay by Presto Blue Cell Viability Reagent. Cells are seeded in 100 mm dishes, incubated overnight at 37 °C and then treated with 10 μM of PF-06424439 for 72 h. Subsequently, cells are collected for clonogenic survival assay, cell death detection, cell cycle analysis, γ-H2AX staining,and lipid droplets staining.^{<a class="sref" href="#s_ref">[2]</a>}

PF-06424439 reduces plasma triglyceride (TG) and cholesterol levels and decreases nonsignificant in circulating lipids in mice (Ldlr-/-). PF-06424439 shows moderate clearance in rats following intravenous administration and moderate steady-state volume of distribution (Vdss) results in a short half-life.^{<a class="sref" href="#s_ref">[1]</a>}