Synthesis of Targeted Drugs for Treating Breast Cancer
Abstract
New chemotherapeutic agents are needed for the improved treatment of breast cancer. In this proposal, we disclose a new approach to the design of anti-cancer drugs. Our method is to synthesize new drug conjugates that incorporate: (i) a specific breast cancer cell-targeting component; (ii) a rapid cell membrane translocating /nuclear localization moiety and; (iii) the capability to counter multi-drug resistance mediated by P-glycoprotein and related cellular efflux pumps. The conjugates are prepared in a few synthetic steps from available components. The goal is to demonstrate a proof-of- concept of the effectiveness of this multi-functional drug hypothesis. Specific cancer cell-targeted compounds have been prepared from the breast cancer drug doxorubicin. This cytotoxic agent is covalently linked to a synthetic arginine-glycine-aspartic acid peptidomimetic, which recognizes and binds to avb3% integrin. This receptor is overexpressed on the surface of breast cancer metastatic cells and tumors. The design also includes incorporation of the Tat peptide analog, H2Narginine7COOH, as a rapid cell membrane translocation and effective nuclear localization moiety. The new drugs will be evaluated in breast cancer cell-lines in vitro and in vivo using human breast cancer xenografts in nude mice.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2004
- Accession Number
- ADA427066
Entities
People
- Jerald C. Hinshaw
Organizations
- University of Utah