TRI-611 is a brain-penetrant, orally active molecular glue degrader targeting ALK . TRI-611 engages ALK via a distal degron, forms a ternary complex with CRBN, triggers ALK polyubiquitination and degradation, including TKI-resistant ALK fusion proteins. TRI-611 inhibits ALK downstream signaling pathways, induces anti-proliferative effects in ALK-positive cancer cells. TRI-611 induces regression of ALK-positive non-small cell lung cancer tumors in preclinical xenograft models . TRI-611 can be used for the research of ALK-positive non-small cell lung cancer , including TKI-refractory tumors and central nervous system metastases.
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