The Design, Synthesis, and Biological Evaluation of New Paclitaxel Analogs With the Ability to Evade Efflux by P-Glycoprotein
Abstract
Paclitaxel, a cytotoxic agent originally isolated fro the bark of the Pacific Yew, has been developed as an effective chemotherapeutic drug, Sadly however, the treatment of cancer with paclitaxel often results in the development of drug resistance. Furthermore, few current chemotherapeutics are able to cross the blood brain barrier leaving victims of brain cancer few viable treatment alternatives. P-glycoproteins are non-specific transmembrane transporter proteins that are associated with specialized normal tissue barriers, for example the blood brain barrier, and are generally over expressed in tumor cells. These transporter systems recognize a large variety of structurally and functionally diverse chemical entities and are responsible for increasing efflux and decreasing influx of lipophilic substances. This active efflux by P-glycoprotein is believed to be responsible for the development of drug resistance and also the lack of brain uptake. This research focuses on strategies to by-pass P-glycoprotein efflux in order to deliver active, structurally modified paclitaxel analogues to the drug resistant breast cancer cells and/or brain cancer cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2004
- Accession Number
- ADA425654
Entities
People
- Brandon J. Turunen
- Gunda I. Georg
Organizations
- University of Kansas