ArticleJournal of medicinal chemistry2016
Discovery of (R)-2-(6-Methoxynaphthalen-2-yl)butanoic Acid as a Potent and Selective Aldo-keto Reductase 1C3 Inhibitor.
Article in Journal of medicinal chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 40 citations in OpenAlex.
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- Mechanistic Elucidation and Stereochemical Consequences of Alternative Binding of Alkenyl Substrates by Engineered Arylmalonate Decarboxylase.Journal of the American Chemical Society · 2025Article
- Role of Human Aldo-Keto Reductases and Nuclear Factor Erythroid 2-Related Factor 2 in the Metabolic Activation of 1,8-Dinitropyrene and Its Metabolite 1-Amino-8-nitropyrene via Nitroreduction in Human Lung Cells.Chemical research in toxicology · 2025Article
- Discovery and Optimization of a Covalent AKR1C3 Inhibitor.Journal of medicinal chemistry · 2025Article
- Specific and potent inhibition of steroid hormone pre-receptor regulator AKR1C2 by perfluorooctanoic acid: Implications for androgen metabolism.The Journal of steroid biochemistry and molecular biology · 2025Article
- Coumarin-Based Aldo-Keto Reductase Family 1C (AKR1C) 2 and 3 Inhibitors.ChemMedChem · 2024Article
- Review
- 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
- Naproxen-Derived New Compound Inhibits the NF-κB, MAPK and PI3K/Akt Signaling Pathways Synergistically with Resveratrol in RAW264.7 Cells.Molecules (Basel, Switzerland) · 2023Article
- Role of Human Aldo-Keto Reductases and Nuclear Factor Erythroid 2-Related Factor 2 in the Metabolic Activation of 1-Nitropyrene via Nitroreduction in Human Lung Cells.Chemical research in toxicology · 2023Article
- Role of Human Aldo-Keto Reductases in the Nitroreduction of 1-Nitropyrene and 1,8-Dinitropyrene.Chemical research in toxicology · 2022Article
- 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
- Conversion of Classical and 11-Oxygenated Androgens by Insulin-Induced AKR1C3 in a Model of Human PCOS Adipocytes.Endocrinology · 2022Article
- Preparation and Synthetic Application of Naproxen-Containing Diaryliodonium Salts.Molecules (Basel, Switzerland) · 2021Article
- The Structural Basis for Nonsteroidal Anti-Inflammatory Drug Inhibition of Human Dihydrofolate Reductase.Journal of medicinal chemistry · 2020Article
- Intracrinology-revisited and prostate cancer.The Journal of steroid biochemistry and molecular biology · 2020Review
- Intracrine androgen biosynthesis and drug resistance.Cancer drug resistance (Alhambra, Calif.) · 2020Review
- A Mansonone Derivative Coupled with Monoclonal Antibody 4D5-Modified Chitosan Inhibit AKR1C3 to Treat Castration-Resistant Prostate Cancer.International journal of nanomedicine · 2020Article
- A 3-(4-nitronaphthen-1-yl) amino-benzoate analog as a bifunctional AKR1C3 inhibitor and AR antagonist: Head to head comparison with other advanced AKR1C3 targeted therapeutics.The Journal of steroid biochemistry and molecular biology · 2019Article
- Potent and Highly Selective Aldo-Keto Reductase 1C3 (AKR1C3) Inhibitors Act as Chemotherapeutic Potentiators in Acute Myeloid Leukemia and T-Cell Acute Lymphoblastic Leukemia.Journal of medicinal chemistry · 2019Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Type 5 17β-hydroxysteroid dehydrogenase, aldo-keto reductase 1C3 (AKR1C3) converts Δ(4)-androstene-3,17-dione and 5α-androstane-3,17-dione to testosterone (T) and 5α-dihydrotestosterone, respectively, in castration resistant prostate cancer (CRPC). In CRPC, AKR1C3 is implicated in drug resistance, and enzalutamide drug resistance can be surmounted by indomethacin a potent inhibitor of AKR1C3. We examined a series of naproxen analogues and find that (R)-2-(6-methoxynaphthalen-2-yl)butanoic acid (in which the methyl group of R-naproxen was replaced by an ethyl group) acts as a potent AKR1C3 inhibitor that displays selectivity for AKR1C3 over other AKR1C enzymes. This compound was devoid of inhibitory activity on COX isozymes and blocked AKR1C3 mediated production of T and induction of PSA in LNCaP-AKR1C3 cells as a model of a CRPC cell line. R-Profens are substrate selective COX-2 inhibitors and block the oxygenation of endocannabinoids and in the context of advanced prostate cancer R-profens could inhibit intratumoral androgen synthesis and act as analgesics for metastatic disease.
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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.