CORVALLIS, Ore. - A novel anti-cancer compound created by chemists at Oregon State University has moved into phase one clinical trials and may have promise in treating certain types of solid tumors, such as those found in ovarian or breast cancer.
The compound, called dehydroepothilone, might be useful for some of the same types of cancers that are now often treated with taxol, a drug originally extracted from yew trees that has grown into a $2 billion annual industry. But the new compound discovered at OSU may be less toxic than taxol, could work better and might be suited to some tumors that are resistant to taxol.
"The in-vitro and animal tests conducted so far are very encouraging about the efficacy of dehydroepothilone," said James White, a distinguished professor emeritus of chemistry at OSU and an expert on the chemical synthesis of complex natural products. "It will be several years before clinical trials can confirm its safety and usefulness as an anti-cancer drug."
The compound created by OSU chemists belongs to the epothilone drug family, a group of compounds originally found in soil bacteria. These chemicals were at first of interest as an antibiotic, and later found to have some anti-cancer properties, White said.
OSU researchers, including doctoral candidate Kurt Sundermann and post-doctoral student Rich Carter, first found a way to chemically synthesize epothilone, and then created an analog that does not exist in nature, but appears to be even more effective. This process is called "rational" drug design, in which the general chemical structure of a compound is defined, and then sometimes tweaked to create novel compounds for medical applications.
"Rational drug design has been done less frequently in recent decades, as pharmaceutical companies used different methods to create and search for new drugs," White said. "But this approach now seems to be regaining interest."
The new dehydroepothilone compound taps into some of the same biochemistry that makes taxol a useful chemotherapeutic drug, White said. There's a certain site on a protein that taxol binds to, causing the formation and then stabilization of "microtubules." For some forms of cancer, it is the disassociation of these microtubules that begins a biological process that culminates in cancer.
"By understanding the structural details about this binding site, which is the same one used by epothilone, we were able to create a new compound that binds even more strongly," White said. "This may produce even more stability than taxol does. Epothilones also provide different characteristics such as better absorption in-vivo."
This field of study is sufficiently promising, White said, that other large pharmaceutical companies are now working on similar compounds. OSU has patented and licensed its discovery of dehydroepothilone, and a California biotechnology company is conducting the beginning clinical trials.
James White, 541-737-2173