poziotinib and Chordoma

We describe the design of a set of inhibitors to investigate the relationship between cyclin G associated kinase (GAK) and epidermal growth factor receptor (EGFR) in chordoma bone cancers. These compounds were characterized both in vitro and using in cell target engagement assays. The most potent chordoma inhibitors were further characterized in a kinome-wide screen demonstrating narrow spectrum profiles. While we observed a direct correlation between EGFR and antiproliferative effects on chordoma, GAK inhibition appeared to have only a limited effect.

Topics: Aminoquinolines; Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Chordoma; Drug Design; ErbB Receptors; HEK293 Cells; Humans; Intracellular Signaling Peptides and Proteins; Molecular Docking Simulation; Protein Binding; Protein Kinase Inhibitors; Protein Serine-Threonine Kinases; Quinazolines