| Literature DB >> 26165155 |
Bainan Wu1, Si Wang1, Surya K De1, Elisa Barile1, Bridget A Quinn2, Irina Zharkikh1, Angela Purves1, John L Stebbins1, Robert G Oshima1, Paul B Fisher2, Maurizio Pellecchia1.
Abstract
The development of novel, targeted delivery agents for anti-cancer therapies requires the design and optimization of potent and selective tumor-targeting agents that are stable and amenable to conjugation with chemotherapeutic drugs. While short peptides represent potentially an excellent platform for these purposes, they often get degraded and are eliminated too rapidly in vivo. In this study, we used a combination of nuclear magnetic resonance-guided structure-activity relationships along with biochemical and cellular studies to derive a novel tumor-homing agent, named 123B9, targeting the EphA2 tyrosine kinase receptor ligand-binding domain. Conjugating 123B9 to the chemotherapeutic drug paclitaxel (PTX) via a stable linker results in an agent that is significantly more effective than the unconjugated drug in both a pancreatic cancer xenograft model and a melanoma lung colonization and metastases model. Hence, 123B9 could represent a promising strategy for the development of novel targeted therapies for cancer.Entities:
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Year: 2015 PMID： 26165155 PMCID： PMC4515144 DOI： 10.1016/j.chembiol.2015.06.011
Source DB: PubMed Journal: Chem Biol ISSN： 1074-5521