1616785-52-4Relevant articles and documents
Design, synthesis and bioevaluation of an EphA2 receptor-based targeted delivery system
Barile, Elisa,Wang, Si,Das, Swadesh K.,Noberini, Roberta,Dahl, Russell,Stebbins, John L.,Pasquale, Elena B.,Fisher, Paul B.,Pellecchia, Maurizio
, p. 1403 - 1412 (2014/07/21)
Because of its overexpression in a range of solid tumors, the EphA2 receptor is a validated target for cancer therapeutics. We recently described a new targeted delivery system based on specific EphA2-targeting peptides conjugated with the chemotherapeutic agent paclitaxel. Here, we investigate the chemical determinants responsible for the stability and degradation of these agents in plasma. Introducing modifications in both the peptide and the linker between the peptide and paclitaxel resulted in drug conjugates that are both long-lived in rat plasma and that markedly decrease tumor size in a prostate cancer xenograft model compared with paclitaxel alone treatment. These studies identify critical rate-limiting degradation sites on the peptide-drug conjugates, enabling the design of agents with increased stability and efficacy. These results provide support for our central hypothesis that peptide-drug conjugates targeting EphA2 represent an innovative and potentially effective strategy to selectively deliver cytotoxic drugs to cancer cells. Ready, aim, fire! We investigated the chemical determinants responsible for the stability and degradation in plasma of an EphA2-based targeted delivery system that is constituted by receptor-targeting peptides conjugated with paclitaxel. We demonstrate that our agents are both long-lived in plasma and markedly decrease tumor size in a prostate cancer xenograft model.
