Sarki Abdulkadir, Targeting the "Undruggable" MYC Protein
For decades, researchers have known that the MYC protein is implicated in more than half of all cancers, including breast, brain, and prostate. However, it has remained an elusive target as its structure has been considered “undruggable.”
Unlike previous efforts, Sarki Adbulkadir, MD, PhD, John T. Grayhack Professor of Urologic Research and director of the Center for Urologic Oncology at the Feinberg School of Medicine, has identified a novel way to screen and identify compounds that would be more likely to successfully target MYC in animals.
In fact, he and his colleagues have identified a number of compounds that effectively block MYC activity in vivo. Contrary to the typical research protocol, Abdulkadir and his team first evaluated a molecule’s potential for blocking MYC before testing in cell lines and subsequently tested its tolerance in mice.
After discovering that blocking MYC activity was feasible, they identified a novel small molecule, MYC inhibitor 361 (MYCi361), which showed initial promise in suppressing in vivo tumor growth in mice. Because it was not well tolerated, a more refined analog, MYCi975, was designed to maintain its efficacy with fewer side effects. The results to date were published last fall in the journal Cancer Cell.
NewCures, Northwestern’s biomedical accelerator that focuses on advancing the development of novel therapeutics, has further supported the development of the identified compounds (known generally as MYCi) and the modification of these compounds to increase specificity and efficacy.
The work with NewCures led to a research collaboration agreement with a major pharmaceutical partner with efforts dedicated to identifying an ideal clinical indication and devising a formulation for effective drug delivery. These steps will take the project closer to potential human studies.
Abdulkadir and his colleagues also had previously participated in INVOForward – a mentorship program to explore value proposition and commercialization strategies for Northwestern biomedical commercialization projects.
“We are attacking a protein that’s involved in the majority of all cancer types,” Abdulkadir said. “If we are successful, the implications are going to be really big. These will be new-in-class molecules. Our compounds will actually enhance the effectiveness of immunotherapy. We can change those tumor types from being nonresponsive to responsive with our compounds.”