Colorectal cancer (CRC) is one of the most commonly diagnosed cancer types and Traf2- and Nck-interacting kinase (TNIK) has been thought as a potential target for CRC treatment. Herein we report the discovery and structure–activity relationship (SAR) of benzo[d]oxazol-2(3H)-one derivatives as a new class of TNIK inhibitors. The most potent compound 8g showed an IC₅₀ value of 0.050 μM against TNIK. It effectively suppressed proliferation and migration of colorectal cancer cells. Western blot analysis indicated that 8g could inhibit aberrant transcription activation of Wnt signaling. Collectively, this study provides a potential lead compound for subsequent drug discovery targeting TNIK.

结直肠癌 (CRC) 是最常诊断的癌症类型之一，Traf2 和 Nck 相互作用激酶 (TNIK) 已被认为是 CRC 治疗的潜在目标。在此，我们报告了苯并[ d ]oxazol-2(3 H )-one 衍生物作为一类新型 TNIK 抑制剂的发现和构效关系 (SAR) 。最有效的化合物8 g对 TNIK的 IC ₅₀值为 0.050 μM。它有效地抑制了结直肠癌细胞的增殖和迁移。蛋白质印迹分析表明8 g可以抑制 Wnt 信号的异常转录激活。总的来说，这项研究为后续针对 TNIK 的药物发现提供了潜在的先导化合物。