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AACR Annual Meeting 2026

April 17–22, 2026 · San Diego · 2418 items

← Medicinal chemistry beyond KRAS: CDK2, WEE1, SERD

TRI-611

5 people · 5 posts · 2 abstracts

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Records
Drug / trialReadoutSetting
TRI-611TRI-611An early code on the floorPhase 1 / preclinical border
Other cases in this chapter
Evidence
4618
TRI-611, a development stage molecular glue degrader of ALK for the treatment of ALK-positive NSCLC including central nervous system metastases

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, Hari B. Kamadurai, Aravind Prasad Medikonda, Duncan E. Nunes, Tim J. Wigle, Maolin Yu, Aleksandra Zagulyaeva, Christine Zarate, Kathleen I. Seyb, Patrick Trojer, Vito J. Palombella

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5787
TRI-611, a development stage molecular glue degrader of ALK, promotes the degradation of TKI-resistant ALK fusion proteins and leads to regression of ALK TKI-refractory tumors

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, Hari B. Kamadurai, Aravind Prasad Medikonda, Duncan E. Nunes, Tim J. Wigle, Maolin Yu, Aleksandra Zagulyaeva, Christine Zarate, Lauren Highfield, Nobuyuki Kondo, Aaron N. Hata, Kenneth Ngo, Jisu Lee, Prafulla C. Gokhale, Kathleen I. Seyb, Patrick Trojer, Vito J. Palombella

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Floor
Oct 8Thu
  1. Nature Reviews Drug Discovery66

    Molecular glue targets ALK resistance

    Conery et al. report in Nature the discovery and preclinical characterization of TRI-611, a selective, brain-penetrant molecular glue degrader that targets ALK fusion proteins in non-small-cell lung cancer, including tyrosine kinase inhibitor-resistant variants. The approach aims to address acquired resistance driven by ALK kinase domain mutations, TKI toxicity, and limited CNS penetration that hinders treatment of brain metastases. Further preclinical and clinical development would follow.

    Why it matters: Molecular glue degrader offers a new way to overcome ALK TKI resistance and CNS penetration limits in NSCLC.

    TRI-611ALKNo engagement yet
Sep 18Fri
  1. Nature62

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

    TRI-611, a brain-penetrant molecular glue degrader, bridges the ALK kinase domain and the CRL4 adaptor CRBN through a degron interface distinct from the kinase active site, yielding proteome-wide selectivity. It degrades all ALK fusion protein forms tested, including wild-type and TKI-resistant versions, driving regression of subcutaneous and intracranial tumour models of ALK-positive NSCLC, alone and synergistically with ALK TKIs. It is described as the first clinical-stage molecular glue degrader targeting an oncogenic gene fusion.

    Why it matters: It offers an orthogonal, degradation-based option for ALK-positive NSCLC after progression on approved TKIs.

    Same topic TRI-611 · 5 peopleALKNo engagement yet
Apr 20Mon
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