ArticleJournal of medicinal chemistry2013
Development of potent and selective indomethacin analogues for the inhibition of AKR1C3 (Type 5 17β-hydroxysteroid dehydrogenase/prostaglandin F synthase) in castrate-resistant prostate cancer.
Article in Journal of medicinal chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
57 citing papers in PubMed, 94 citations in OpenAlex.
- From biomass to bioactivity:RSC advances · 2026Article
- Natural simple coumarins and their interaction with AKR1C3: implications for overcoming chemoradioresistance in gastrointestinal carcinomas.Medical oncology (Northwood, London, England) · 2026Article
- Androgen receptor reactivation in castration-resistant prostate cancer: mechanisms, epigenetic adaptation, and therapeutic vulnerabilities.Frontiers in oncology · 2026Review
- The structural basis of aldo-keto reductase 1C3 inhibition by 17α-picolyl and 17(Journal of enzyme inhibition and medicinal chemistry · 2025Article
- Metabolic activation of flunitrazepam via nitroreduction mediated by aldo-keto reductase 1C3.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Discovery and Optimization of a Covalent AKR1C3 Inhibitor.Journal of medicinal chemistry · 2025Article
- Polygenic anti-cancer activity ofToxicology reports · 2024Article
- LX1 Dual Targets AR Variants and AKR1C3 in Advanced Prostate Cancer Therapy.Cancer research · 2024Article
- Coumarin-Based Aldo-Keto Reductase Family 1C (AKR1C) 2 and 3 Inhibitors.ChemMedChem · 2024Article
- AKR1C3 in carcinomas: from multifaceted roles to therapeutic strategies.Frontiers in pharmacology · 2024Review
- Review
- Prostaglandin FWorld journal of gastroenterology · 2023Article
- Targeting sex steroid biosynthesis for breast and prostate cancer therapy.Nature reviews. Cancer · 2023Review
- 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
- X-ray structure of human aldo-keto reductase 1C3 in complex with a bile acid fused tetrazole inhibitor: experimental validation, molecular docking and structural analysis.RSC medicinal chemistry · 2023Article
- Acquisition of Immune Privilege in GBM Tumors: Role of Prostaglandins and Bile Salts.International journal of molecular sciences · 2023Article
- Aldo-keto reductase family member C3 (AKR1C3) promotes hepatocellular carcinoma cell growth by producing prostaglandin F2α.Oncology research · 2023Article
- Triflamides and Triflimides: Synthesis and Applications.Molecules (Basel, Switzerland) · 2022Review
- Characterization of the major single nucleotide polymorphic variants of aldo-keto reductase 1C3 (type 5 17β-hydroxysteroid dehydrogenase).The Journal of steroid biochemistry and molecular biology · 2022Article
- Aldo-Keto Reductases and Cancer Drug Resistance.Pharmacological reviews · 2021Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Castrate-resistant prostate cancer (CRPC) is a fatal, metastatic form of prostate cancer. CRPC is characterized by reactivation of the androgen axis due to changes in androgen receptor signaling and/or adaptive intratumoral androgen biosynthesis. AKR1C3 is upregulated in CRPC where it catalyzes the formation of potent androgens. This makes AKR1C3 a target for the treatment of CRPC. AKR1C3 inhibitors should not inhibit AKR1C1/AKR1C2, which inactivate 5α-dihydrotestosterone. Indomethacin, used to inhibit cyclooxygenase, also inhibits AKR1C3 and displays selectivity over AKR1C1/AKR1C2. Parallel synthetic strategies were used to generate libraries of indomethacin analogues, which exhibit reduced cyclooxygenase inhibitory activity but retain AKR1C3 inhibitory potency and selectivity. The lead compounds inhibited AKR1C3 with nanomolar potency, displayed >100-fold selectivity over AKR1C1/AKR1C2, and blocked testosterone formation in LNCaP-AKR1C3 cells. The AKR1C3·NADP(+)·2'-des-methyl-indomethacin crystal structure was determined, and it revealed a unique inhibitor binding mode. The compounds reported are promising agents for the development of therapeutics for CRPC.
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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.