{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE329nnn/GSE329452/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE329452"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"TRI-611, a selective, brain-penetrant molecular glue degrader of ALK","description":"Tyrosine 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.","dates":{"publication":"2026/08/01"},"accession":"GSE329452","cross_references":{"GSM":["GSM9704332","GSM9704321","GSM9704331","GSM9704320","GSM9704330","GSM9704325","GSM9704324","GSM9704323","GSM9704333","GSM9704322","GSM9704329","GSM9704318","GSM9704328","GSM9704317","GSM9704327","GSM9704316","GSM9704326","GSM9704319"],"GPL":["20301"],"GSE":["329452"],"taxon":["Homo sapiens"]}}