Peptide inhibitors permanently block cancer's cJun protein

Scientists have found promising new drug candidates that can permanently block a cancer protein called cJun. This protein is known to be difficult to target with drugs. cJun is a transcription factor, which means it helps control gene activity. It can become overactive in cancer, leading to uncontrolled cell growth. Attempts to create drugs that target transcription factors have often been unsuccessful. Recently, researchers at the University of Bath explored using small protein fragments called peptides to block these problematic targets. The researchers used a new method called the Transcription Block Survival (TBS) assay. This technique allows the testing of many peptides to find those that can effectively switch off cancer-driving transcription factors. They previously discovered reversible inhibitors of cJun but have now developed peptides that bind tightly and permanently. Dr. Andy Brennan, one of the study's authors, compared the peptide inhibitor to a harpoon that securely attaches to cJun. This stops cJun from pairing with DNA, which is essential for its function. The team tested the peptides in living cells to confirm their effectiveness. Jody Mason, another researcher, explained that many drugs that work in lab settings fail in real cells. Their new screening method assesses how well these peptides work in more realistic conditions, overcoming challenges faced by traditional drugs. Having demonstrated that the peptides can penetrate cancer cells and effectively target cJun, the next step for researchers is to test these inhibitors in preclinical cancer models. They hope to find more drug candidates for other cancer targets that have been considered "undruggable."