6TRY

Crystal structure of human Aldehyde dehydrogenase 1A3 in complex with MF13 inhibitor compound

6TRY の概要

• エントリーDOI: 10.2210/pdb6try/pdb
• 分子名称: Aldehyde dehydrogenase family 1 member A3, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, 8-(4-chlorophenyl)-2-phenyl-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: 114383.07

構造登録者

Gelardi, E.L.M.,Garavaglia, S. (登録日: 2019-12-19, 公開日: 2021-01-13, 最終更新日: 2025-10-01)

主引用文献

Quattrini, L.,Gelardi, E.L.M.,Petrarolo, G.,Colombo, G.,Ferraris, D.M.,Picarazzi, F.,Rizzi, M.,Garavaglia, S.,La Motta, C.
Progress in the Field of Aldehyde Dehydrogenase Inhibitors: Novel Imidazo[1,2- a ]pyridines against the 1A Family.
Acs Med.Chem.Lett., 11:963-970, 2020

PubMed Abstract: Members of the aldehyde dehydrogenase 1A family are commonly acknowledged as hallmarks of cancer stem cells, and their overexpression is significantly associated with poor prognosis in different types of malignancies. Accordingly, treatments targeting these enzymes may represent a successful strategy to fight cancer. In this work we describe a novel series of imidazo[1,2-]pyridines, designed as aldehyde dehydrogenase inhibitors by means of a structure-based optimization of a previously developed lead. The novel compounds were evaluated for their activity and selectivity against the three isoforms of the ALDH1A family and investigated through crystallization and modeling studies for their ability to interact with the catalytic site of the 1A3 isoform. Compound emerged as the first in class submicromolar competitive inhibitor of the target enzyme.

PubMed: 32435412
DOI: 10.1021/acsmedchemlett.9b00686

実験手法

X-RAY DIFFRACTION (2.9 Å)