NU collaborators from the Center for Molecular Innovation and Drug Discovery (CMIDD), the Robert H. Lurie Comprehensive Cancer Center (RHLCCC), and the Feinberg School of Medicine (FSM), have received funding from the National Cancer Institute (NCI) to develop compounds that may lead to an entirely new treatment for Acute Myeloid Leukemia (AML).
This grant, which will provide $1.58 million over the next three years, will support medicinal chemistry, molecular modeling, and biological testing to optimize small molecule CXCR4-receptor antagonists and agonists. This receptor is known to play a critical role in myriad diseases including cancer, HIV infectivity, and inflammation.
Although the CXCR4 receptor has been widely studied, researchers have been unable to identify small molecule agonists of the receptor, which has made it difficult to fully examine its role in fundamental biological processes.
However, by harnessing new in silico techniques, Dr. Rama Mishra, CMIDD Cheminformatics Specialist, was able to identify a number of compounds that appeared to bind the receptor. Subsequent in vitro screenings completed by Dr. Richard Miller, Professor of Pharmacology, confirmed an unprecedented finding that many of these compounds acted as agonists towards CXCR4 and that these agonists actually increased the sensitivity of AML cells to drug therapy.
“We have developed an entirely new class of CXCR4 modulators. We expect that these compounds will be very valuable as molecular probes to better understand CXCR4 pharmacology and ultimately, may lead to new advances in therapeutics for AML and other cancers,” said Dr. Gary Schiltz, Assistant Research Professor in CMIDD and PI of the multi-investigator grant. “This is an excellent example of how collaborators with different expertise can carry out truly innovative research.”
With these funds, Dr. Schiltz (CMIDD) will coordinate research efforts with co-PIs Drs. Leonidas Platanias (RHLCCC) and Richard Miller (FSM) to more fully study the biological effects of CXCR4 antagonists and agonists, create more potent and effective compounds, and ultimately develop the basis for an entirely new way to treat AML.