2. Academic Validation
  3. Identification of small molecule activators targeting TYK2 pseudokinase domain

Identification of small molecule activators targeting TYK2 pseudokinase domain

  • Bioorg Med Chem Lett. 2025 Aug 1:123:130233. doi: 10.1016/j.bmcl.2025.130233.
Hirokazu Matsumoto 1,  Tien-Cheng Wang 2,  Haruka Taniguchi 2,  Yu Nishioka 2,  Mariko Hatakeyama 2,  Takayoshi Kinoshita 3,  Masaaki Sawa 2
Affiliations

Affiliations

  • 1 Carna Biosciences, Inc., Kobe 650-0047, Japan. Electronic address: hirokazu.matsumoto@dd.carnabio.com.
  • 2 Carna Biosciences, Inc., Kobe 650-0047, Japan.
  • 3 Graduate School of Science, Osaka Metropolitan University, Osaka 599-8570, Japan.
PMID: 40209917 DOI: 10.1016/j.bmcl.2025.130233
Abstract

Tyrosine kinase 2 (Tyk2) plays a crucial role in both adaptive and innate immune responses. The catalytic activity of the Tyk2 JH1 kinase domain is controlled by the Tyk2 JH2 pseudokinase domain and stabilized to maintain its inactive state until the upstream receptor activations. Here, we report the discovery of aminopyridine analogs as novel Tyk2 activators through structural modification of a known JH2 binder. Compound 16b demonstrated a dose-dependent increase in Tyk2 enzymatic activity.

Keywords

Activator; Pseudokinase domain; TYK2.

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