6TE5

Crystal structure of human Aldehyde dehydrogenase 1A3 in complex with LQ43 inhibitor compound

6TE5 の概要

• エントリーDOI: 10.2210/pdb6te5/pdb
• 関連するPDBエントリー: 6S6W
• 分子名称: Aldehyde dehydrogenase family 1 member A3, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, 6-(3,5-dimethoxyphenyl)-2-(4-methoxyphenyl)imidazo[1,2-a]pyridine, ... (5 entities in total)
• 機能のキーワード: dehydrogenase isoenzyme aldh1a3 selective inhibitor high grade glioma, oxidoreductase
• 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: 114494.33

構造登録者

Gelardi, E.L.M.,Garavaglia, S. (登録日: 2019-11-11, 公開日: 2020-11-18, 最終更新日: 2025-10-01)

主引用文献

Quattrini, L.,Gelardi, E.L.M.,Coviello, V.,Sartini, S.,Ferraris, D.M.,Mori, M.,Nakano, I.,Garavaglia, S.,La Motta, C.
Imidazo[1,2- a ]pyridine Derivatives as Aldehyde Dehydrogenase Inhibitors: Novel Chemotypes to Target Glioblastoma Stem Cells.
J.Med.Chem., 63:4603-4616, 2020

PubMed Abstract: Glioblastoma multiforme (GBM) is the deadliest form of brain tumor. It is known for its ability to escape the therapeutic options available to date thanks to the presence of a subset of cells endowed with stem-like properties and ability to resist to cytotoxic treatments. As the cytosolic enzyme aldehyde dehydrogenase 1A3 turns out to be overexpressed in these kinds of cells, playing a key role for their vitality, treatments targeting this enzyme may represent a successful strategy to fight GBM. In this work, we describe a novel class of imidazo[1,2-]pyridine derivatives as aldehyde dehydrogenase 1A3 inhibitors, reporting the evidence of their significance as novel drug candidates for the treatment of GBM. Besides showing an interesting functional profile, in terms of activity against the target enzyme and selectivity toward highly homologous isoenzymes, representative examples of the series also showed a nanomolar to picomolar efficacy against patient-derived GBM stem-like cells, thus proving the concept that targeting aldehyde dehydrogenase might represent a novel and promising way to combat GBM by striking its ability to divide immortally.

PubMed: 32223240
DOI: 10.1021/acs.jmedchem.9b01910

実験手法

X-RAY DIFFRACTION (3.25 Å)