7C3N
Crystal structure of JAK3 in complex with Delgocitinib
Summary for 7C3N
| Entry DOI | 10.2210/pdb7c3n/pdb |
| Descriptor | 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) |
| Functional Keywords | inhibitor, transferase, transferase-inihibitor complex, transferase/inihibitor |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 36157.03 |
| Authors | Doi, S.,Otira, T.,Kikuwaka, M.,Nomura, A.,Noji, S.,Adachi, T. (deposition date: 2020-05-13, release date: 2020-06-24, Last modification date: 2024-11-20) |
| Primary citation | 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 Cited by 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: 32511913DOI: 10.1021/acs.jmedchem.0c00450 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.98 Å) |
Structure validation
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