8DHH

DHODH IN COMPLEX WITH LIGAND 29

8DHH の概要

• エントリーDOI: 10.2210/pdb8dhh/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: dihydroorotate dehydrogenase, dhodh, oxidoreductase, inhibitor, 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: 1
• 化学式量合計: 41511.27

構造登録者

Shaffer, P.L. (登録日: 2022-06-27, 公開日: 2022-08-17, 最終更新日: 2023-10-18)

主引用文献

Cisar, J.S.,Pietsch, C.,DeRatt, L.G.,Jacoby, E.,Kazmi, F.,Keohane, C.,Legenski, K.,Matico, R.,Shaffer, P.,Simonnet, Y.,Tanner, A.,Wang, C.Y.,Wang, W.,Attar, R.,Edwards, J.P.,Kuduk, S.D.
N -Heterocyclic 3-Pyridyl Carboxamide Inhibitors of DHODH for the Treatment of Acute Myelogenous Leukemia.
J.Med.Chem., 65:11241-11256, 2022

PubMed Abstract: Acute myelogenous leukemia (AML), a disease of the blood and bone marrow, is characterized by the inability of myeloblasts to differentiate into mature cell types. Dihydroorotate dehydrogenase (DHODH) is an enzyme well-known in the pyrimidine biosynthesis pathway; however, small molecule DHODH inhibitors were recently shown to induce differentiation in multiple AML subtypes. Using virtual screening and structure-based drug design approaches, a new series of N-heterocyclic 3-pyridyl carboxamide DHODH inhibitors were discovered. Two lead compounds, and , have potent biochemical and cellular DHODH activity, favorable physicochemical properties, and efficacy in a preclinical model of AML.

PubMed: 35925768
DOI: 10.1021/acs.jmedchem.2c00788

実験手法

X-RAY DIFFRACTION (2.02 Å)