ArticleChemico-biological interactions2011
Discovery of novel regulators of aldehyde dehydrogenase isoenzymes.
Article in Chemico-biological interactions, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 41 citations in OpenAlex.
- A Novel Salicylaldehyde Dehydrogenase from Alpine Soil Metagenome Reveals a Unique Catalytic Mechanism.Applied biochemistry and biotechnology · 2025Article
- Pharmacological agents targeting drug-tolerant persister cells in cancer.Pharmacological research · 2024Review
- Development of substituted benzimidazoles as inhibitors of human aldehyde dehydrogenase 1A isoenzymes.Chemico-biological interactions · 2024Article
- ALDEFLUOR activity, ALDH isoforms, and their clinical significance in cancers.Journal of enzyme inhibition and medicinal chemistry · 2023Article
- Identification of a peptide ligand for human ALDH3A1 through peptide phage display: Prediction and characterization of protein interaction sites and inhibition of ALDH3A1 enzymatic activity.Frontiers in molecular biosciences · 2023Article
- A Novel ALDH1A1 Inhibitor Blocks Platinum-Induced Senescence and Stemness in Ovarian Cancer.Cancers · 2022Article
- Computational Investigation of Structural Basis for Enhanced Binding of Isoflavone Analogues with Mitochondrial Aldehyde Dehydrogenase.ACS omega · 2022Article
- Design, Synthesis, Biological Evaluation and In Silico Study of Benzyloxybenzaldehyde Derivatives as Selective ALDH1A3 Inhibitors.Molecules (Basel, Switzerland) · 2021Article
- Development of 2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one inhibitors of aldehyde dehydrogenase 1A (ALDH1A) as potential adjuncts to ovarian cancer chemotherapy.European journal of medicinal chemistry · 2021Article
- In vitro metabolic profile and drug-drug interaction assessment of secnidazole, a high-dose 5-nitroimidazole antibiotic for the treatment of bacterial vaginosis.Pharmacology research & perspectives · 2020Article
- Identification of Specific Lysines and Arginines That Mediate Angiomotin Membrane Association.ACS omega · 2019Article
- Structure-Based Optimization of a Novel Class of Aldehyde Dehydrogenase 1A (ALDH1A) Subfamily-Selective Inhibitors as Potential Adjuncts to Ovarian Cancer Chemotherapy.Journal of medicinal chemistry · 2018Article
- Different specificities of two aldehyde dehydrogenases fromBioscience reports · 2017Article
- Inhibition of the Aldehyde Dehydrogenase 1/2 Family by Psoralen and Coumarin Derivatives.Journal of medicinal chemistry · 2017Article
- Structure and mechanism of benzaldehyde dehydrogenase from Pseudomonas putida ATCC 12633, a member of the Class 3 aldehyde dehydrogenase superfamily.Protein engineering, design & selection : PEDS · 2017Article
- Development of a high-throughput in vitro assay to identify selective inhibitors for human ALDH1A1.Chemico-biological interactions · 2015Article
- Discovery of a series of aromatic lactones as ALDH1/2-directed inhibitors.Chemico-biological interactions · 2015Article
- N,N-diethylaminobenzaldehyde (DEAB) as a substrate and mechanism-based inhibitor for human ALDH isoenzymes.Chemico-biological interactions · 2015Article
- Article
- Characterization of two distinct structural classes of selective aldehyde dehydrogenase 1A1 inhibitors.Journal of medicinal chemistry · 2015Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Over the past three years we have been involved in high-throughput screening in an effort to discover novel small molecular modulators of aldehyde dehydrogenase (ALDH) activity. In particular, we have been interested in both the activation and inhibition of the three commonly studied isoenzymes, ALDH1A1, ALDH2 and ALDH3A1, as their distinct, yet overlapping substrate specificities, present a particularly difficult challenge for inhibitor discovery and design. Activation of ALDH2 has been shown to benefit cardiovascular outcome following periods of ischemia and renewed interest in specific inhibition of ALDH2 has application for alcohol aversion therapy, and more recently, in cocaine addiction. In contrast, inhibition of either ALDH1A1 or ALDH3A1 has application in cancer treatments where the isoenzymes are commonly over-expressed and serve as markers for cancer stem cells. We are taking two distinct approaches for these screens: in vitro enzyme activity screens using chemical libraries and virtual computational screens using the structures of the target enzymes as filters for identifying potential inhibitors, followed by in vitro testing of their ability to inhibit their intended targets. We have identified selective inhibitors of each of these three isoenzymes with inhibition constants in the high nanomolar to low micromolar range from these screening procedures. Together, these inhibitors provide proof for concept that selective inhibition of these broad specificity general detoxication enzymes through small molecule discovery and design is possible.
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Registered trials
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