6TE5
Crystal structure of human Aldehyde dehydrogenase 1A3 in complex with LQ43 inhibitor compound
Summary for 6TE5
| Entry DOI | 10.2210/pdb6te5/pdb |
| Related | 6S6W |
| Descriptor | 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) |
| 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 | 114494.33 |
| Authors | Gelardi, E.L.M.,Garavaglia, S. (deposition date: 2019-11-11, release date: 2020-11-18, Last modification date: 2025-10-01) |
| Primary citation | 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 Cited by 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: 32223240DOI: 10.1021/acs.jmedchem.9b01910 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.25 Å) |
Structure validation
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