ArticleACS medicinal chemistry letters2019
Bioisosteres of Indomethacin as Inhibitors of Aldo-Keto Reductase 1C3.
Article in ACS medicinal chemistry letters, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 50 citations in OpenAlex.
- Fluorescent Isostere (Journal of medicinal chemistry · 2025Article
- Discovery and Optimization of a Covalent AKR1C3 Inhibitor.Journal of medicinal chemistry · 2025Article
- Quantum Evaluation of a Comprehensive Set of Carboxylic Acid Bioisosteres: Gas versus Solvated Phases.ACS omega · 2025Article
- Article
- Coumarin-Based Aldo-Keto Reductase Family 1C (AKR1C) 2 and 3 Inhibitors.ChemMedChem · 2024Article
- AI Based Discovery of a New AKR1C3 Inhibitor for Anticancer Applications.ACS medicinal chemistry letters · 2024Article
- Intramolecular interactions and the neutral loss of ammonia from collisionally activated, protonated ω-aminoalkyl-3-hydroxyfurazans.European journal of mass spectrometry (Chichester, England) · 2024Article
- AKR1C3 in carcinomas: from multifaceted roles to therapeutic strategies.Frontiers in pharmacology · 2024Review
- Aldo-Keto Reductase 1C3 Inhibitor Prodrug Improves Pharmacokinetic Profile and Demonstrates In Vivo Efficacy in a Prostate Cancer Xenograft Model.Journal of medicinal chemistry · 2023Article
- Computational modeling studies reveal the origin of the binding preference of 3-(3,4-di hydroisoquinolin-2(1H)-ylsulfonyl)benzoic acids for AKR1C3 over its isoforms.Protein science : a publication of the Protein Society · 2022Article
- Targeting Acute Myelogenous Leukemia Using Potent Human Dihydroorotate Dehydrogenase Inhibitors Based on the 2-Hydroxypyrazolo[1,5-Journal of medicinal chemistry · 2021Article
- AKR1C3 is a biomarker and druggable target for oropharyngeal tumors.Cellular oncology (Dordrecht, Netherlands) · 2021Article
- Intracrine androgen biosynthesis and drug resistance.Cancer drug resistance (Alhambra, Calif.) · 2020Review
- Article
- Use of the 4-Hydroxytriazole Moiety as a Bioisosteric Tool in the Development of Ionotropic Glutamate Receptor Ligands.Journal of medicinal chemistry · 2019Article
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aldo-keto reductase 1C3 (AKR1C3) is an attractive target in drug design for its role in resistance to anticancer therapy. Several nonsteroidal anti-inflammatory drugs such as indomethacin are known to inhibit AKR1C3 in a nonselective manner because of COX-off target effects. Here we designed two indomethacin analogues by proposing a bioisosteric connection between the indomethacin carboxylic acid function and either hydroxyfurazan or hydroxy triazole rings. Both compounds were found to target AKR1C3 in a selective manner. In particular, hydroxyfurazan derivative is highly selective for AKR1C3 over the 1C2 isoform (up to 90-times more) and inactive on COX enzymes. High-resolution crystal structure of its complex with AKR1C3 shed light onto the binding mode of the new inhibitors. In cell-based assays (on colorectal and prostate cancer cells), the two indomethacin analogues showed higher potency than indomethacin. Therefore, these two AKR1C3 inhibitors can be used to provide further insight into the role of AKR1C3 in cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.