Drug Pipeline Brimming With Projects, Some Close to Testing

Published May 20, 2009

At academic health centers, there are drug discovery programs – and then there are drug discovery programs. Georgetown University Medical Center (GUMC) has the latter—emphasis added.

Less than three years after it was started by Milton Brown, MD, PhD, GUMC’s program has 60 projects in the pipeline, collaboration with 35 investigators, 20 patents, and nine new molecules – potential drugs - that have gone from concept into preclinical testing.

“In the past, academia defined drug discovery as someone in chemistry working with someone in biology on a single project chemical,” says Brown. “What we offer is a centralized translational resource that will go out into the GUMC community and empower it. We help investigators translate basic science into clinical opportunity.

“And we are just scratching the surface,” he says. “There are still many projects out there that need our support.”

The program has grown so big, with specialized faculty working with state-of-the-art equipment on discrete areas of drug design – cell assays, chemical synthesis, scale-up chemistry, preclinical animal models, and a process known as absorption, distribution, metabolism and excretion/toxicology – that one ongoing project is to develop computer software to manage all the data being produced and make it available to all investigators.

“There is a lot going on, but I just ride a horse really fast,” says Brown with a laugh.

As an example of innovation, he talks about small molecules being tested preclinically that “fluoresce” green in human tissues when they are activated – a new concept designed to tell how effective a novel agent may be.

One is a compound derived from the leaf of the Mediterranean curry plant, which produces oil that has been used in traditional medicine as an anti-inflammatory. The agent, discovered in collaboration with GUMC biochemist Partha Banerjee, PhD, turns on a tumor suppressor gene in prostate cancer. “We can track the activity of the molecule in prostate cells in the laboratory and in preclinical models and see that it works,” Brown says.

Another compound, developed with radiation oncologist Anatoly Dritschilo, MD, and radiation medicine researcher Mira Jung, PhD, is intended for prostate, lung and pancreatic cancers. But the twist with this agent is that it could also be used to help diagnose cancer. The selective histone deacetylase (HDAC) inhibitor, with its fluorescent tag, is absorbed by epithelial cells, which means that it can preferentially treat tumors that overproduce epithelial cells, and the green light emitted could be “read” by a scanner to sense tumor masses and drug delivery to the tumor. So along with development of the agent, the drug design team will collaborate with engineers to design a specific scanner to be used as a diagnostic tool. “This is the perfect example of a theranostic – a therapeutic and diagnostic agent rolled into one. This is very exciting.”

The third drug close to human testing is a compound discovered by pediatric oncologist Jeff Toretsky, MD, which appears to be active against the childhood cancer, Ewing’s sarcoma. Brown and his staff were able to make the compound more active against cancer cells and then they produced enough to test it in multiple preclinical models.

Brown can only take these agents so far. To test them in humans, investigators need to partner with other academic medical centers, biotech or pharmaceutical companies to conduct phase 0/I/II clinical trials. To do so at GUMC would constitute a conflict of interest, he says. “This is a good problem to have,” Brown says. “I think we will have many more of them in the future.”

By Renee Twombly, GUMC Communications