COMBRETASTATIN A-4 ANALOGUES FOR CANCER THERAPY

Invention Summary:

Cancer is one of the most common human diseases, and leads to about 12% of all deaths worldwide. Mitotic inhibitors such as paclitaxel, which is a tubulin-binding compound that disrupts the formation of mitotic spindles, are widely used for the treatment of cancer, and have achieved great commercial successes. However, these clinically used anti-tubulin drugs often face severe limitations such as neural and systemic toxicity, multiple side effects, induction of drug resistance, and complex synthetic pathways and isolation methods.

Combretastatin A-4 (CA-4) is a potent tubulin inhibitor with a simple chemical structure, a broad spectrum of activity, lack of recognition by the multidrug resistance (MDR) pump, and reported anti-angiogenesis activity. Unfortunately, its structural instability has limited the compound’s in vivo efficacy.

The inventors have discovered novel CA-4 analogues with good structural stability, higher anti-tubulin activity, remarkable cancer cell specificity, strong cytotoxicity, good bioavailability, and easy synthesis and isolation methods. Furthermore, the cytotoxic effects of these compounds were shown to be comparable in a variety of cancer cell lines versus their multiple drug resistant (MDR+) subclones, suggesting that these compounds can overcome cancer cell drug resistance resulting from the presence of the MDR pump.

In addition, a detailed evaluation conducted by the NIH-National Center Institute (NCI) Developmental Therapeutic Program (DTP) demonstrated uniformly good growth inhibitory activity of one of these compounds, T115, across the 60-cell line panel, with exceptionally strong activity in non-small cell lung cancer cell lines.

Market Applications:

  • Pharmaceutical treatment for hyperproliferative disorders such as:
    • Cancer
    • Restenosis
    • Inflammation
    • Hyperproliferation at a site of mechanical injury to an arterial wall produced by treatment of an atherosclerotic lesion by angioplasty
  • Medical device that is coated with pharmaceutical compounds to treat the above hyperproliferative disorders.

Intellectual Property & Development Status:

  • Published PCT application: PCT/US2005/038655
  • United States patent number 8,143,299 granted on March 27, 2012
Rutgers ID: S04-29
Category(s):
Life Sciences
Therapeutics
Contact:
Shan Wan
Senior Licensing Manager
(848) 932-4468
shanwan@rutgers.edu
Inventors:
William Welsh
Youyi Peng
Xin Wang
Susan Keenan
Qiang Zhang
Sonia Arora
Keywords:
Oncology