2. Academic Validation
  3. Design and synthesis of novel thiazole-derivatives as potent ALK5 inhibitors

Design and synthesis of novel thiazole-derivatives as potent ALK5 inhibitors

  • Bioorg Med Chem Lett. 2024 May 16:108:129797. doi: 10.1016/j.bmcl.2024.129797.
Mai Arai 1,  Mitsuharu Hanada 2,  Hideki Moriyama 2,  Hiroshi Ohmoto 2,  Takahiro Miyake 2,  Kazuhito Naka 3,  Masaaki Sawa 2
Affiliations

Affiliations

  • 1 Carna Biosciences, Inc., 1-5-5 Minatojima-Minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan. Electronic address: mai.arai@dd.carnabio.com.
  • 2 Carna Biosciences, Inc., 1-5-5 Minatojima-Minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
  • 3 Department of Stem Cell Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
PMID: 38759932 DOI: 10.1016/j.bmcl.2024.129797
Abstract

TGF-β is an immunosuppressive cytokine and plays a key role in progression of Cancer by inducing immunosuppression in tumor microenvironment. Therefore, inhibition of TGF-β signaling pathway may provide a potential therapeutic intervention in treating cancers. Herein, we report the discovery of a series of novel thiazole derivatives as potent inhibitors of ALK5, a serine-threonine kinase which is responsible for TGF-β signal transduction. Compound 29b was identified as a potent inhibitor of ALK5 with an IC50 value of 3.7 nM with an excellent kinase selectivity.

Keywords

ALK5; Activin receptor-like kinases; Kinase inhibitor; TGF-β; TGFβR1.

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