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

TRI-611 is the first clinical-stage molecular glue degrader targeting ALK fusion proteins, achieving tumor regression in ALK-positive NSCLC models.

• Why it matters: Current ALK inhibitors face limitations due to resistance, leaving a critical need for alternative therapies that can target resistant or wild-type ALK fusion proteins in lung cancer patients.
• What they did: Researchers developed TRI-611, a brain-penetrant molecule that promotes degradation of ALK fusion proteins by bridging ALK kinase domains and CRBN, and tested its efficacy in cell and tumor models.
• The result: TRI-611 effectively degrades all ALK fusion variants, including resistant forms, and enhances tumor regression when combined with ALK TKIs, broadening treatment options for ALK-positive NSCLC.