ARTICLE | Distillery Therapeutics

Therapeutics: EPH receptor A2 (EPHA2)

August 6, 2015 7:00 AM UTC

In vitro and mouse studies suggest conjugates of EPHA2-targeting peptidomimetics and paclitaxel could help treat EPHA2-positive cancers. EPHA2 expression in tumors is associated with increased metastatic behavior. Screening of a panel of peptides with N-terminal synthetic tyrosine mimetics identified a peptidomimetic that bound EPHA2 in vitro with a Kd of 4 μM and had greater stability in rat plasma than EPHA2-binding peptides with N-terminal tyrosines. In a mouse xenograft model of pancreatic cancer, paclitaxel conjugated to the peptidomimetic decreased tumor growth compared with unconjugated paclitaxel. In a mouse xenograft model of metastatic melanoma, the paclitaxel-peptidomimetic conjugate decreased tumor growth compared with Abraxane or no treatment. Next steps could include testing the long-term in vivo safety profile of the conjugate...