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

Nature Medical/Healthcare AI Andrew R. Conery, Daniel S. La, Artyom A. Alekseyenko, David Marcoux, Aaron G. Bart, Matt L. Harlow, Patrick R. Arsenault, Nico R. Cantone, Rebecca L. Casaubon, Alexander Constan, Hari B. Kamadurai, Aravind Prasad Medikonda, Duncan E. Nunes, Hannah Szeto, Tim J. Wigle, Maolin Yu, Aleksandra Zagulyaeva, Christine M. Zarate, Lauren Highfield, Nobuyuki Kondo, Aaron N. Hata, Kenneth Ngo, Jisu Lee, Prafulla C. Gokhale, Caroline Germa, Kathleen I. Seyb, Patrick Trojer, Vito J. Palombella 2026-09-09

TL;DR - TRI-611 is a selective, brain-penetrant molecular glue degrader that targets ALK fusion proteins. Its preclinical anti-tumour activity suggests a potential new treatment strategy for ALK-positive non-small-cell lung cancer.

TRI-611 induces ALK fusion protein degradation through a previously undescribed CRBN recruitment motif.
Brain penetration could be relevant to treating ALK-positive cancers involving the central nervous system.
The reported efficacy is preclinical, so clinical safety and effectiveness remain unestablished.

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