7C3N

Crystal structure of JAK3 in complex with Delgocitinib

7C3N の概要

• エントリーDOI: 10.2210/pdb7c3n/pdb
• 分子名称: Tyrosine-protein kinase JAK3, 3-[(3S,4R)-3-methyl-7-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,7-diazaspiro[3.4]octan-1-yl]-3-oxidanylidene-propanenitrile (3 entities in total)
• 機能のキーワード: inhibitor, transferase, transferase-inihibitor complex, transferase/inihibitor
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 36157.03

構造登録者

Doi, S.,Otira, T.,Kikuwaka, M.,Nomura, A.,Noji, S.,Adachi, T. (登録日: 2020-05-13, 公開日: 2020-06-24, 最終更新日: 2023-11-29)

主引用文献

Noji, S.,Hara, Y.,Miura, T.,Yamanaka, H.,Maeda, K.,Hori, A.,Yamamoto, H.,Obika, S.,Inoue, M.,Hase, Y.,Orita, T.,Doi, S.,Adachi, T.,Tanimoto, A.,Oki, C.,Kimoto, Y.,Ogawa, Y.,Negoro, T.,Hashimoto, H.,Shiozaki, M.
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., 63:7163-7185, 2020

PubMed 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 (-), 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.

PubMed: 32511913
DOI: 10.1021/acs.jmedchem.0c00450

実験手法

X-RAY DIFFRACTION (1.98 Å)