Synthesis and anti-tumor activity of imidazopyrazines as TAK1 inhibitors

  • Eur J Med Chem. 2019 Feb 1:163:660-670. doi: 10.1016/j.ejmech.2018.12.025.
Seok Jong Kang  1 ,  Jung Wuk Lee  2 ,  Shin Hyuck Chung  2 ,  Sun Young Jang  1 ,  Jaeyul Choi  3 ,  Kwee Hyun Suh  3 ,  Young Hoon Kim  3 ,  Young Jin Ham  3 ,  Kyung Hoon Min  4
Affiliations
  • 1. College of Pharmacy, Chung-Ang University, Seoul, 06974, Republic of Korea; Department of Drug Discovery, Hanmi Research Center, Gyeonggi-do, 18469, Republic of Korea.
  • 2. College of Pharmacy, Chung-Ang University, Seoul, 06974, Republic of Korea.
  • 3. Department of Drug Discovery, Hanmi Research Center, Gyeonggi-do, 18469, Republic of Korea.
  • 4. College of Pharmacy, Chung-Ang University, Seoul, 06974, Republic of Korea. Electronic address: [email protected].
PMID: 30576901 DOI: 10.1016/j.ejmech.2018.12.025
Abstract

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.

Keywords
Colon cancer; Imidazopyrazine; TAK1.