Medicinal Chemistry Graduate Plays Instrumental Role in Promising Cancer Research
Before graduating with his doctorate in medicinal chemistry from the College of Pharmacy last August, Brandt Huddle, PhD, played an instrumental role in the development of a new therapeutic compound for cancer, CM39. The compound inhibits the ability of a key enzyme, aldehyde dehydrogenase (ALDH), to promote chemotherapy resistance in a small pool of cells linked to ovarian cancer.
For women diagnosed with ovarian cancer, the mortality rate is high, due to this cell pool’s hardiness against chemo, helped by the ALDH enzyme, which allows it to recur and metastasize.
“We were able to get a crystal structure of the enzyme with our lead compound, which is like a picture of the drug binding with the protein we’re targeting,” says Dr. Huddle, who published his findings in the Journal of Medicinal Chemistry (in collaboration with Magee-Womens Research Institute in Pittsburgh and Indiana University Medical School). “So, based on that picture, we were able to make modifications to our compound that made it bind better to the target. In theory, that should make [CM39] more effective as a treatment for chemoresistant cancer.”
Dr. Huddle, who is now a research chemist at Weill Cornell Medical College in Manhattan, credits much of his research success to his then thesis advisor, Scott Larsen, PhD, Joseph Burckhalter Collegiate Research Professor of Medicinal Chemistry and Co-director of the Vahlteich Medicinal Chemistry Core. “Dr. Larsen ran a fantastic group, and all his projects were of high impact,” says Dr. Huddle. “He gave me a pretty long leash to do what I wanted, but was always available if I had a question. Or if he noticed me going in a wrong direction, he would correct course on that. I received really great training from him, and I’m very grateful for that.”
The Vahlteich Medicinal Chemistry Core, where Dr. Huddle did his graduate work, is uniquely suited for such highly specialized research projects.
A cure for ovarian cancer is still years away, but the CM39 target opens the door to further research for more potent, selective inhibitors. “Preparations for mouse studies are underway and the project team at the Vahlteich Medicinal Chemistry Core continues to optimize compounds for in vivo exposure,” says Dr. Huddle, whose work is still primarily concerned with therapeutics for cancer.
According to Dr. Larsen, Brandt Huddle represents exactly what is expected from his graduate students. “My students should already be trained to be project leaders by the time they leave here,” he says. “Brandt is certainly in that camp. He basically did everything on that project, working directly with the biologist, analyzing the data, designing the compounds. So it’s really exciting that he got this job with a prestigious institution like Cornell.”