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

TRI-611 is a potent, brain-penetrant molecular glue degrader (MGD) of ALK fusion proteins with the potential to address this need .

TRI-611 promotes the proximity of the ALK kinase domain and CRBN via a unique degron interface distal from the kinase active site. The unique binding interface of TRI-611 leads to selectivity across the proteome including known CRBN neo-substrates and other kinases. TRI-611 treatment induces degradation of all forms of oncogenic ALK fusion proteins, including TKI-resistant mutated versions of ALK, leading to regression of cell line and patient-derived subcutaneous and intracranial tumour models of ALK-positive NSCLC.