University of Chicago Scientists discover way to target undruggable molecules involved in cancer

23 Nov 2022

~Scientists at UChicago have announced the development of an innovative method for creating synthetic molecules that can target previously "undruggable" proteins known to be active in cancer and other diseases~

National, November 22nd, 2022: A group of University of Chicago scientists announced the development of a novel method for creating synthetic molecules capable of targeting these previously "untargetable" transcription factors. The discovery, which was published on October 27 in Nature Biotechnology, has implications for drugs and treatments as well as tools for better understanding cancer biology. UChicago made a breakthrough while cancer researchers worldwide have been looking for a way to target transcription factors for decades.

While known for a long time that tumors use these proteins to grow out of control, their unique configurations meant that they had earned the moniker "undruggable" for more than 30 years.
“Doctors have had a hit list of transcription factors for decades, but we have lacked a way to target them,” said UChicago chemist Raymond Moellering, the senior author on the study. “This work sets the stage for letting us go directly for any transcription factor. If you ask clinicians what they want in order to treat cancer, it’s a way to inhibit Myc. Using the traditional drugs on transcription factors is like trying to get a foothold on a 50-foot vertical cliff. Right away when we ran the gels, we could see that we had cracked the code for the right configuration.”

The researchers wanted to be able to tailor the molecule to target a variety of transcription factors. They created a customizable skeleton; based on their findings, that skeleton could be 'reprogrammed' to target a different DNA sequence and thus affect a different disease-causing transcription factor. This is due in part to the fact that transcription factors are involved in everything from aging to diabetes to autoimmune disease.


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