GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE329nnn/GSE329452/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE329452GEOGSEfalseTRI-611, a selective, brain-penetrant molecular glue degrader of ALKTyrosine kinase inhibitors (TKIs) targeting Anaplastic Lymphoma Kinase (ALK) have transformed the treatment landscape of ALK fusion-positive non-small cell lung carcinoma (NSCLC), but limited options for patients who progress on approved TKIs highlight a continued need for an orthogonal therapeutic approach. 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. TRI-611 can be combined with orthosteric ALK TKIs, achieving synergistic and durable tumour regressions. TRI-611 represents the first example of a clinical stage MGD targeting an oncogenic gene fusion and has the potential to expand the arsenal of therapeutic options for ALK-positive NSCLC patients.2026/08/01GSE329452GSM9704332GSM9704321GSM9704331GSM9704320GSM9704330GSM9704325GSM9704324GSM9704323GSM9704322GSM9704333GSM9704329GSM9704318GSM9704328GSM9704317GSM9704327GSM9704316GSM9704326GSM970431920301329452Homo sapiens