6O3I

Crystal Structure of Human IDO1 bound to navoximod (NLG-919)

6O3I の概要

• エントリーDOI: 10.2210/pdb6o3i/pdb
• 分子名称: Indoleamine 2,3-dioxygenase 1, PROTOPORPHYRIN IX CONTAINING FE, trans-4-{(1R)-2-[(5S)-6-fluoro-5H-imidazo[5,1-a]isoindol-5-yl]-1-hydroxyethyl}cyclohexan-1-ol, ... (4 entities in total)
• 機能のキーワード: dioxygenase, tryptophan, ido, tdo, oxidoreductase-inhibitor complex, oxidoreductase/inhibitor
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 96686.32

構造登録者

Harris, S.F.,Oh, A. (登録日: 2019-02-26, 公開日: 2019-07-17, 最終更新日: 2019-08-07)

主引用文献

Kumar, S.,Waldo, J.P.,Jaipuri, F.A.,Marcinowicz, A.,Van Allen, C.,Adams, J.,Kesharwani, T.,Zhang, X.,Metz, R.,Oh, A.J.,Harris, S.F.,Mautino, M.R.
Discovery of Clinical Candidate (1R,4r)-4-((R)-2-((S)-6-Fluoro-5H-imidazo[5,1-a]isoindol-5-yl)-1-hydroxyethyl)cyclohexan-1-ol (Navoximod), a Potent and Selective Inhibitor of Indoleamine 2,3-Dioxygenase 1.
J.Med.Chem., 62:6705-6733, 2019

PubMed Abstract: A novel class of 5-substituted 5-imidazo[5,1-]isoindoles are described as potent inhibitors of indoleamine 2,3-dioxygenase 1 (IDO1). A structure-based drug design approach was used to elaborate the 5-imidazo[5,1-]isoindole core and to improve potency and pharmacological properties. Suitably placed hydrophobic and polar functional groups in the lead molecule allowed improvement of IDO1 inhibitory activity while minimizing off-target liabilities. Structure-activity relationship studies focused on optimizing IDO1 inhibition potency and a pharmacokinetic profile amenable to oral dosing while controlling CYP450 and hERG inhibitory properties.

PubMed: 31264862
DOI: 10.1021/acs.jmedchem.9b00662

実験手法

X-RAY DIFFRACTION (2.69 Å)