Molecular display allows physical linkage of a protein to its coding nucleic acid.Techniques in this area promise great utilities in protein drug discovery.Applying these techniques in directed protein evolution,we have discovered drug leads that bind and antagonize the function of vascular endothelial growth factor receptor 2 (VEGFR2).Inhibitors to human VEGFR2 (KDR) with 10-200nM affinities were selected by using mRNA display from a library (1013 variants) based on the tenth human fibronectin type Ⅲ domain (10Fn3) scaffold.Subsequently,a single KDR binding clone (Kd=1 lnM) was subjected to affinity maturation.This yielded improved KDR binding molecules with affinities ranging from 0.06 to 2nM.Molecules with dual binding specificities (human/mouse) were also isolated by using both KDR and Flk-1 (mouse VEGFR2) as targets in selection.Proteins encoded by the selected clones bound VEGFR2-expressing cells and inhibited their VEGF-dependent proliferation.Our results demonstrate the potential of these inhibitors in the development of anti-angiogenesis therapeutics.Recent advances in molecular display and protein drug discovery in our laboratory will be presented.