| 体内研究: |
G-5555 exhibits low blood clearance and an acceptable half-life. Good oral exposure (AUC=30 μM•h) and high oral bioavailability (F=80%) are achieved. In an H292 non-small cell lunger cancer (NSCLC) xenograft study in mice, G-5555 inhibits phosphorylation of the PAK1/2 downstream substrate mitogen-activated protein kinase 1 (MEK1) S298 and, when administered at an oral dose of 25 mg/kg b.i.d., imparts 60% tumor growth inhibition in this model13 and a PAK1 amplified breast cancer xenograft model, MDAMB-175. |