STAT3 is a promising therapeutic target for the treatment of gastric cancer, which is one of the most common solid tumors worldwide. In the previous works, we discovered a series of novel STAT3 inhibitors bearing an imidazo[1,2-a] pyridine scaffold. In order to improve the metabolic stability of these compounds, herein we performed a systematic structural optimization leading to a bioactive inhibitor 42, which demonstrated significant effects on inhibiting the growth, migration and invasion of human gastric cancer cells lines (AGS and MGC-803). Meanwhile, it was able to block the phosphorylation and dimerization of STAT3 at low micromolar concentration. Furthermore, compound 42 obviously suppressed tumor growth in MGC-803 derived xenograft mouse model, suggesting that it deserves further exploration as a promising anti-cancer agent for advanced gastric cancer.

STAT3 是治疗胃癌的有前途的治疗靶点，胃癌是世界上最常见的实体瘤之一。在之前的工作中，我们发现了一系列带有咪唑并 [1,2- a ] 吡啶支架的新型 STAT3 抑制剂。为了提高这些化合物的代谢稳定性，我们在此进行了系统的结构优化，从而产生了一种生物活性抑制剂42，该抑制剂对抑制人胃癌细胞系（AGS 和 MGC-803）的生长、迁移和侵袭具有显着影响。 . 同时，它能够在低微摩尔浓度下阻断STAT3的磷酸化和二聚化。此外，化合物42在 MGC-803 衍生的异种移植小鼠模型中明显抑制肿瘤生长，表明它作为晚期胃癌的有前途的抗癌剂值得进一步探索。