Prof. Maurizio Pellecchia and his colleagues at the University of California, Riverside have developed peptide-based EphA2 agonistic agents that have nanomolar activities. These agents, having the same mechanism of action as the natural (ephrinA1-Fc) ligands, effectively degrade EphA2 receptors and delay cell migration in key cancer cell lines. These agonistic agents may be effective therapeutics that may result in less unwanted side effects that have been observed in the clinic with ADCs targeting EphA2. Fig. 1 Top, X-ray structure of EphA2 in complex with UCR agent.. Bottom, Treatment with ephrinA1-Fc or UCR agent 135H12 on an orthotopic mouse model of prostate cancer with PC-3-GFP cells (n = 5 mice per treatment group). The mean fluorescence intensity related to metastases detected at day 7 from mice in each group, control (the solvent formulation used for 135H12), ephrinA1-Fc treated, 135H12 treated. Error bars represent standard deviation. ** p < 0.01.