TRI-611 

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^[1][2][3].

TRI-611 在无细胞生化/生物物理实验中可同等有效地促进 CRBN 与野生型 ALK 及 ALK^{L1196M/G1202R} 复合突变体蛋白的相互作用，以及后续的多聚泛素化修饰^[1]。
TRI-611 可有效靶向经改造的 Ba/F3 细胞中所有 30 种受试的 EML4-ALK 突变蛋白，包括 TKI 耐药变体^[1]。
TRI-611 可强效抑制携带多种 ALK TKI 耐药等位基因的 ALK 阳性非小细胞肺癌 (NSCLC) 细胞系的增殖^[1]。
TRI-611 可在 ALK 阳性细胞中诱导 EML4-ALK 融合蛋白及致癌性跨膜 ALK 发生快速、强效且持久的 CRBN 依赖性降解，化合物处理 1-2 小时内即可达到>90%的最大降解率，且停药后的恢复半衰期超过 15 小时^[2]。
TRI-611 可促进 ALK 融合等位基因 (包括 TKI 耐药突变体) 的泛素化与降解，且对 ALK 融合驱动的 NSCLC 细胞系产生的表型影响比 ALK TKI 更广泛^[3]。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

在小鼠药效研究中，TRI-611 可使对 ALK TKIs 无应答的 CRISPR 编辑 EML4-ALK 突变型 NCI-H3122 细胞的皮下异种移植瘤消退^[1]。
TRI-611 具有口服生物利用度及血脑屏障穿透性，每日口服给药可在 ALK 阳性 NSCLC 的皮下和颅内异种移植模型中实现内源性 EML4-ALK 的深度且持久降解，以及肿瘤消退^[2][3]。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

404.38

C₂₁H₁₆N₄O₅

3117940-39-0

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Andrew R. Conery, et al. Abstract 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. Cancer Res (2026) 86 (7_Supplement): 5787.

  [2]. Andrew R. Conery, et al. Abstract 4618: TRI-611, a development stage molecular glue degrader of ALK for the treatment of ALK-positive NSCLC including central nervous system metastases. Cancer Res (2026) 86 (7_Supplement): 4618.

  [3]. Andrew R. Conery, et al. Abstract B064: TRI-611, a selective, CNS-penetrant molecular glue degrader of ALK with anti-tumor activity against preclinical models of ALK-fusion positive non-small cell lung cancer including kinase inhibitor refractory tumors. Mol Cancer Ther (2025) 24 (10_Supplement): B064.