College of Pharmacy, Chung-Ang University, Seoul, 06974, Republic of Korea; Department of Drug Discovery, Hanmi Research Center, Gyeonggi-do, 18469, Republic of Korea.
College of Pharmacy, Chung-Ang University, Seoul, 06974, Republic of Korea.
Eur J Med Chem. 2019 Feb 1;163:660-670. doi: 10.1016/j.ejmech.2018.12.025. Epub 2018 Dec 13.
Transforming growth factor-β activated kinase-1 (TAK1) is a potential therapeutic target for cancers and inflammatory diseases. We synthesized a series of novel imidazopyrazine derivatives, which were found to exhibit potent inhibitory effect against TAK1. Compound 22a, which possesses a good pharmacokinetic profile, showed excellent in vitro kinase activity and significant in vivo efficacy in mice xenografted with SW620, a KRAS-dependent colon cancer cell line.
转化生长因子-β 激活激酶 1（TAK1）是癌症和炎症性疾病的潜在治疗靶点。我们合成了一系列新型咪唑并吡嗪衍生物，发现它们对 TAK1 具有很强的抑制作用。具有良好药代动力学特性的化合物 22a 表现出优异的体外激酶活性和在携带 KRAS 依赖性结肠癌细胞系 SW620 的小鼠异种移植模型中的显著体内疗效。
