6TRY

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

Summary for 6TRY

• Entry DOI: 10.2210/pdb6try/pdb
• Descriptor: Aldehyde dehydrogenase family 1 member A3, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, 8-(4-chlorophenyl)-2-phenyl-imidazo[1,2-a]pyridine, ... (5 entities in total)
• Functional Keywords: dehydrogenase isoenzyme aldh1a3 selective inhibitor high grade glioma, oxidoreductase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 114383.07

Authors

Gelardi, E.L.M.,Garavaglia, S. (deposition date: 2019-12-19, release date: 2021-01-13, Last modification date: 2025-10-01)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.9 Å)