Stanford researchers engineer a molecule that turns lymphoma driver into a self-destruct switch
A two-part compound created by Stanford scientists rewires the lymphoma-promoting protein BCL6 to trigger cancer cell death, eradicating aggressive tumors in mice within 11 days.
Stanford scientists have built a two-headed small molecule named TCIP3 that links the lymphoma-driving transcription factor BCL6 to the acetyltransferases P300 and CBP. By attaching to BCL6 and adding acetyl tags, the drug disables BCL6’s repression of death-related genes and actively promotes their expression, effectively turning the cancer’s own engine against it. Crystallographic analysis revealed the compound functions as a molecular glue, creating additional contacts that lock the proteins together and boost potency.
In laboratory tests, TCIP3 killed lymphoma cells at very low concentrations, and in mice implanted with human diffuse large B-cell lymphoma, twice-daily treatment caused complete tumor disappearance within 11 days with no clear signs of toxicity. The researchers note the strategy may extend to other oncogenic proteins and could have relevance for autoimmune diseases that also rely on BCL6. Further chemical refinement and testing in additional animal models are required before human trials can be considered.
Why it matters
It demonstrates a novel way to convert a cancer-promoting protein into a trigger for tumor death, offering a potential new therapeutic avenue.
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