2. Academic Validation
  3. Discovery of a Janus Kinase Inhibitor Bearing a Highly Three-Dimensional Spiro Scaffold: JTE-052 (Delgocitinib) as a New Dermatological Agent to Treat Inflammatory Skin Disorders

Discovery of a Janus Kinase Inhibitor Bearing a Highly Three-Dimensional Spiro Scaffold: JTE-052 (Delgocitinib) as a New Dermatological Agent to Treat Inflammatory Skin Disorders

  • J Med Chem. 2020 Jul 9;63(13):7163-7185. doi: 10.1021/acs.jmedchem.0c00450.
Satoru Noji 1,  Yoshinori Hara 1,  Tomoya Miura 1,  Hiroshi Yamanaka 1,  Katsuya Maeda 1,  Akimi Hori 1,  Hiroshi Yamamoto 1,  Shingo Obika 1,  Masafumi Inoue 1,  Yasunori Hase 1,  Takuya Orita 1,  Satoki Doi 1,  Tsuyoshi Adachi 1,  Atsuo Tanimoto 2,  Chika Oki 2,  Yukari Kimoto 2,  Yoshihiro Ogawa 2,  Tamotsu Negoro 3,  Hiromasa Hashimoto 1,  Makoto Shiozaki 1
Affiliations

Affiliations

  • 1 Chemical Research Laboratories, Central Pharmaceutical Research Institute, Japan Tobacco Inc., 1-1 Murasaki-cho, Takatsuki, Osaka 569-1125, Japan.
  • 2 Biological Pharmacological Research Laboratories, Central Pharmaceutical Research Institute, Japan Tobacco Inc., 1-1 Murasaki-cho, Takatsuki, Osaka 569-1125, Japan.
  • 3 Drug Metabolism & Pharmacokinetics Research Laboratories, Central Pharmaceutical Research Institute, Japan Tobacco Inc., 1-1 Murasaki-cho, Takatsuki, Osaka 569-1125, Japan.
PMID: 32511913 DOI: 10.1021/acs.jmedchem.0c00450
Abstract

Dermatologic disorders such as atopic dermatitis arise from genetic and environmental causes and are complex and multifactorial in nature. Among possible risk factors, aberrant immunological reactions are one of the leading etiologies. Immunosuppressive agents including topical Steroids are common treatments for these disorders. Despite their reliability in clinical settings, topical Steroids display side effects, typified by skin thinning. Accordingly, there is a need for alternate effective and well-tolerated therapies. As part of our efforts to investigate new immunomodulators, we have developed a series of JAK inhibitors, which incorporate novel three-dimensional spiro motifs and unexpectedly possess both excellent physicochemical properties and antidermatitis efficacy in the animal models. One of these compounds, JTE-052 (ent-60), also known as delgocitinib, has been shown to be effective and well-tolerated in human clinical trials and has recently been approved in Japan for the treatment of atopic dermatitis as the first drug among Janus kinase inhibitors.

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