The Tyrosine kinase EPHA2 (Ephrin type-A receptor 2) receptor plays an important role in cancer development and treatment resistance. Efforts to target EPHA2 therapeutically, to advance drug discovery, or explore its biological functions are hindered by a lack of comprehensive structural information. We performed FMOPhore analysis on twentyfour different ligands binding to the EPHA2 receptor to rationalize the key hotspots of its binding site.