8VHM

Structure of DHODH in Complex with Fragment 2

これはPDB形式変換不可エントリーです。

8VHM の概要

• エントリーDOI: 10.2210/pdb8vhm/pdb
• 分子名称: Dihydroorotate dehydrogenase (quinone), mitochondrial, FLAVIN MONONUCLEOTIDE, OROTIC ACID, ... (8 entities in total)
• 機能のキーワード: dhodh, oxidoreductase, inhibitor, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase/oxidoreductase inhibitor
• 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: 41343.64

構造登録者

Shaffer, P.L. (登録日: 2024-01-02, 公開日: 2024-04-03)

主引用文献

DeRatt, L.G.,Pietsch, E.C.,Cisar, J.S.,Jacoby, E.,Kazmi, F.,Matico, R.,Shaffer, P.,Tanner, A.,Wang, W.,Attar, R.,Edwards, J.P.,Kuduk, S.D.
Discovery of Alternative Binding Poses through Fragment-Based Identification of DHODH Inhibitors.
Acs Med.Chem.Lett., 15:381-387, 2024

PubMed Abstract: Dihydroorotate dehydrogenase (DHODH) is a mitochondrial enzyme that affects many aspects essential to cell proliferation and survival. Recently, DHODH has been identified as a potential target for acute myeloid leukemia therapy. Herein, we describe the identification of potent DHODH inhibitors through a scaffold hopping approach emanating from a fragment screen followed by structure-based drug design to further improve the overall profile and reveal an unexpected novel binding mode. Additionally, these compounds had low P-gp efflux ratios, allowing for applications where exposure to the brain would be required.

PubMed: 38505861
DOI: 10.1021/acsmedchemlett.3c00543

実験手法

X-RAY DIFFRACTION (2.26 Å)