ArticleJournal of medicinal chemistry2014
Development of selective inhibitors for aldehyde dehydrogenases based on substituted indole-2,3-diones.
Article in Journal of medicinal chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- A sequence motif enables widespread use of noncanonical redox cofactors in natural enzymes.Nature chemical biology · 2026Article
- Integrating AI in Medicinal Chemistry for Accelerated Drug Discovery: A Comprehensive SAR (CSAR) Optimization Strategy and Discovery of Potent ALDH3A1 Inhibitors.Journal of medicinal chemistry · 2026Article
- Identification and characterization of a novel aldehyde metabolite of WIN18,446 and associated WIN18,446-ALDH1A2 protein adducts using mass spectrometry.Drug metabolism reviews · 2026Article
- A scaffold repositioning approach: dihydroBenzoImidazoTriazineDione (BITD) derivatives as selective ALDH1A1 inhibitors.Molecular diversity · 2026Article
- Development of retinoid nuclear receptor pathway antagonists through targeting aldehyde dehydrogenase 1A3.iScience · 2025Article
- Integrated Approach of Machine Learning and High-Throughput Screening to Identify Chemical Probe Candidates Targeting Aldehyde Dehydrogenases.ACS pharmacology & translational science · 2025Article
- The Benzoxazole Heterocycle: A Comprehensive Review of the Most Recent Medicinal Chemistry Developments of Antiproliferative, Brain-Penetrant, and Anti-inflammatory Agents.Topics in current chemistry (Cham) · 2024Review
- The pathogenic role of retinoid nuclear receptor signaling in cancer and metabolic syndromes.The Journal of experimental medicine · 2024Review
- Identification of Novel Isatin Derivative Bearing a Nitrofuran Moiety as Potent Multi-Isoform Aldehyde Dehydrogenase Inhibitor.Molecules (Basel, Switzerland) · 2024Article
- Pharmacological agents targeting drug-tolerant persister cells in cancer.Pharmacological research · 2024Review
- Human Aldehyde Dehydrogenases: A Superfamily of Similar Yet Different Proteins Highly Related to Cancer.Cancers · 2023Review
- Aldehyde dehydrogenase in solid tumors and other diseases: Potential biomarkers and therapeutic targets.MedComm · 2023Review
- QSAR-based rational discovery of novel substituted-4'-iminospiro[indoline-3,3'-[1,2,5]thiadiazolidinyl]-2-one 1',1'-dioxide with potent in vitro anticancer activity.BMC chemistry · 2019Article
- Identification of Specific Lysines and Arginines That Mediate Angiomotin Membrane Association.ACS omega · 2019Article
- Review
- Discovery of Orally Bioavailable, Quinoline-Based Aldehyde Dehydrogenase 1A1 (ALDH1A1) Inhibitors with Potent Cellular Activity.Journal of medicinal chemistry · 2018Article
- Structural Basis of ALDH1A2 Inhibition by Irreversible and Reversible Small Molecule Inhibitors.ACS chemical biology · 2018Article
- Aldehyde dehydrogenase 1A1 increases NADH levels and promotes tumor growth via glutathione/dihydrolipoic acid-dependent NADOncotarget · 2017Article
- Targeting aldehyde dehydrogenase activity in head and neck squamous cell carcinoma with a novel small molecule inhibitor.Oncotarget · 2017Article
- A High-Content Assay Enables the Automated Screening and Identification of Small Molecules with Specific ALDH1A1-Inhibitory Activity.PloS one · 2017Article
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Authors and funding
5 authors.
Funding
Abstract
Aldehyde dehydrogenases (ALDH) participate in multiple metabolic pathways and have been indicated to play a role in several cancerous disease states. Our laboratory is interested in developing novel and selective ALDH inhibitors. We looked to further work recently published by developing a class of isoenzyme-selective inhibitors using similar indole-2,3-diones that exhibit differential inhibition of ALDH1A1, ALDH2, and ALDH3A1. Kinetic and X-ray crystallography data suggest that these inhibitors are competitive against aldehyde binding, forming direct interactions with active-site cysteine residues. The selectivity is precise in that these compounds appear to interact directly with the catalytic nucleophile, Cys243, in ALDH3A1 but not in ALDH2. In ALDH2, the 3-keto group is surrounded by the adjacent Cys301/303. Surprisingly, the orientation of the interaction changes depending on the nature of the substitutions on the basic indole ring structure and correlates well with the observed structure-activity relationships for each ALDH isoenzyme.
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