TRI-611, a selective, brain-penetrant molecular glue degrader of ALK

TRI-611 is a novel brain-penetrant molecular glue degrader that induces selective degradation of ALK fusion proteins through a previously undescribed CRBN recruitment motif. In preclinical models the compound demonstrated anti-tumour activity against ALK-positive non-small-cell lung cancer, including CNS disease, positioning it as a potential new therapeutic approach for patients who progress on conventional ALK tyrosine kinase inhibitors. The work, published in Nature, provides mechanistic proof-of-concept for targeted protein degradation via a new cereblon-binding mode.