What’s old is new again

PhytoMedical to develop Dartmouth’s forgotten cancer compounds

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PRINCETON, N.J.—In another example of industry-academic collaboration, PhytoMedical Technologies Inc., an early stage, research-based biopharmaceutical company, announced in August that it has entered into an exclusive worldwide license agreement with Dartmouth College to develop a class of innovative compounds that have demonstrated anti-tumor capabilities.

Under the terms of the agreement, PhytoMedical will develop, market and distribute a line of anti-cancer compounds patented in 2001 by Dartmouth chemistry professor Dr. Gordon Gribble. The two parties will expand Gribble's concept of bis-intercalation, or "double-binding," of anti-tumor agents with a cytotoxic affinity for cancer cells, and evaluate these new compounds against several different cancer cell lines, including prostate, lung, brain and bladder cancer. PhytoMedical will pay an undisclosed license fee and milestone payments to Dartmouth.

Although Gribble's project has sat on the shelf since 2001 due to a lack of outside funding, PhytoMedical President and CEO Greg Wujek says the company decided to undertake further development of the compounds after a series of ongoing tests on human cancer cells demonstrated their anti-tumor capabilities. Bis-intercalation stops the replication of DNA, which prevents the growth of cancer cells, resulting in the cells dying.

"The development of Dr. Gribble's compounds holds promise as a potentially entirely new class of compounds to help fight cancer," Wujek says. "Our cancer research collaboration with Dartmouth College adds yet another novel class of compounds to our expanding drug discovery pipeline."

In Gribble's initial published research with graduate student Gary Jaycox, the synthesized compounds were evaluated on their ability to bind to DNA and measured for cytotoxicity against a mouse leukemia cell line. In 2001, a patent was issued based on the success of the research and its promise for the field of cancer treatment.

"Our basic premise of some 20 years ago was that DNA bis-intercalating agents that are linked by a semi-rigid tether would show a powerful advantage over existing conventional intercalators for two reasons," Gribble says. "The problematic 'self-stacking' of typical bis-intercalators would be precluded in our molecules, and the unfavorable entropy cost that is inherent with flexible tethers binding to DNA would be substantially less with our 'semi-rigid' tethers. This premise has been borne out, much to our satisfaction."

Grateful that PhytoMedical will breathe new life into his research findings, Gribble says that such industry-academic collaborations are of great importance in today's current climate of difficult federal funding.

"Moreover, the 'pure science' attitude of academic scientists often leads to research discoveries that might be overlooked or neglected by big pharma," Gribble says.

"Working with Jaycox, our design of semi-rigid bis-intercalators arose from 'playing' in my office with CPK space-filling models of these compounds interacting with a CPK model of DNA. I would expect and hope to see more such collaborations between academic research groups and industry. For a relatively modest price tag, such as one postdoctoral researcher, the rewards can be enormous." DDN

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