South Carolina College of Pharmacy (SCCP) faculty member Campbell McInnes and his company PPI Pharmaceuticals were recently awarded a $225,000 small business technology transfer award to develop technology that can target cancer cells without harming healthy cells.
The National Institutes of Health (NIH) Small Business Technology Transfer (STTR) award will be used to advance REPLACE, a drug discovery technology developed at the University of South Carolina (USC), and further apply it to molecular targets in cancer.
This technology allows for pharmaceutical development against targets previously inaccessible through conventional methods and therefore facilitates next generation cancer therapeutics.
Using computer screening, design, and chemical synthesis, McInnes and his team have developed and applied REPLACE to generate drug-like protein mimetics. These are starting points for novel, anti-cancer therapeutics based on inhibition of protein kinases -- a type of enzyme -- involved in regulation of the cell cycle in cancer cells.
Cancers are dependent on a number of altered molecular pathways typically involving bypassing of normal checkpoints in the cell cycle. Cell cycle inhibitors developed using REPLACE can exploit a concept called “synthetic lethality” where inhibiting the function of a kinase sensitizes a cancer cell which already has a specific defective molecular pathway.
“The result of this is that in theory, only the cancer cell is killed by the treatment and healthy cells are unaffected,” said McInnes, an associate professor of drug discovery and biomedical sciences at SCCP’s USC campus. “Therapies acting in this way should be more effective, much less toxic and have fewer side effects therefore dramatically improving cancer treatment compared to conventional chemotherapies.”
In order to develop cell cycle inhibitors that act very specifically against a precise molecular target, an effective strategy is to block interactions of protein-protein complexes. While such targets lead to more specific inhibitors, they are considerably more challenging to develop.
REPLACE is a strategy which allows the development of drugs for such previously inaccessible protein-protein interaction targets and therefore provides new opportunities to develop very selective inhibitors for cell cycle kinases and many other molecular pathways that become deregulated in cancer.
“Through advances in the understanding of the molecular differences between normal and cancer cells, we aim to exploit new information to design next generation therapeutics for some of the deadliest cancers,” said McInnes. “Our rational design approach applying REPLACE has the potential to provide breakthrough protein mimetic inhibitors that can then be considered as leads for development of more drug-like compounds as targeted cancer therapeutics.”
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