This proof-of-principal work was published in the journal Proceedings of the National Academy of Sciences (Vol. 100, No. 9, April 29, 2003). Intriguingly, the scientists reported that they were able to induce the self-assembly of the complex not only by combining the two substances in the test tube before administration, but also by injecting the two compounds separately into the bloodstream of a mouse, where the compounds found each other and self-assembled into the desired complex.
In both cases, the hybrid molecules had a profound effect on the size of tumors in mouse modelsXshrinking tumors of both Kaposi's sarcoma and colon cancer.
"We were able to show the chemically programmed complex had at least 1,000-fold increase in the therapeutic effect compared with the small molecule alone," said Barbas. "With that came the idea that is this too powerful an approach not to push into human studies."
By the time the study was published, Barbas and Lerner had founded CovX, a privately held company with offices in Dublin, Ireland, and San Diego, CA, to do just that.
Today, two of the hybrid compounds under development by CovX have completed preclinical work with promising results as anti-tumor agents and have been approved for testing in humans. The compound the company calls CVX-045 is currently finishing Phase I trials. CVX-060 is poised to enter Phase 1 trials this month. A third compound to treat diabetes is close behind. By the end of next year, four novel drugs should be in clinical testing. "The Pfizer acquisition will allow us to fully realize the potential of this approach. Within five years we hope to have more than a dozen new drugs in clinical testing," said Barbas
"It has been a dream of mine to develop drugs that make a difference," said Barbas. "I couldn't be more excit
|Contact: Keith McKeown|
Scripps Research Institute