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ID: ALA5247622

Journal: Eur J Med Chem

Title: Structural optimization of Imidazo[1, 2-a]pyridine derivatives for the treatment of gastric cancer via STAT3 signaling pathway.

Authors: Li H, Ouyang S, Zhang Y, Peng K, Fang W, Liu Z, Wang CY, Zhang X, Wang Y.

Abstract: 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.

CiteXplore: 36283181

DOI: 10.1016/j.ejmech.2022.114858