ArticleInvestigational new drugs2014
In vitro and in vivo characterisation of ASP9521: a novel, selective, orally bioavailable inhibitor of 17β-hydroxysteroid dehydrogenase type 5 (17βHSD5; AKR1C3).
Article in Investigational new drugs, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
43 citing papers in PubMed, 56 citations in OpenAlex.
- Safety, tolerability and anti-tumour activity of the androgen biosynthesis inhibitor ASP9521 in patients with metastatic castration-resistant prostate cancer: multi-centre phase I/II study.Investigational new drugs · 2014Trial
- AKR1C3 inhibitors and exploiters for the treatment and therapeutic monitoring of cancer: a patent review (2020-present).Expert opinion on therapeutic patents · 2026Review
- Naringin sensitizes nasopharyngeal carcinoma cells to paclitaxel by inducingThe Journal of international medical research · 2026Article
- AKR1C3-PKM2-oxidative phosphorylation axis drives prostate cancer radioresistance via UBE2T upregulation.Cell death & disease · 2026Article
- Endometrial Metabolism of 17β-Estradiol during the Window of Implantation in Women with Recurrent Implantation Failure.Gynecologic and obstetric investigation · 2026Observational
- Metabolic activation of flunitrazepam via nitroreduction mediated by aldo-keto reductase 1C3.Drug metabolism and disposition: the biological fate of chemicals · 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
- LX1 Dual Targets AR Variants and AKR1C3 in Advanced Prostate Cancer Therapy.Cancer research · 2024Article
- AI Based Discovery of a New AKR1C3 Inhibitor for Anticancer Applications.ACS medicinal chemistry letters · 2024Article
- AKR1C3 in carcinomas: from multifaceted roles to therapeutic strategies.Frontiers in pharmacology · 2024Review
- Targeting sex steroid biosynthesis for breast and prostate cancer therapy.Nature reviews. Cancer · 2023Review
- Exploring the Potential of Sulfur Moieties in Compounds Inhibiting Steroidogenesis.Biomolecules · 2023Article
- 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
- In Silico and In Vitro Assessment of Carbonyl Reductase 1 Inhibition Using ASP9521-A Potent Aldo-Keto Reductase 1C3 Inhibitor with the Potential to Support Anticancer Therapy Using Anthracycline Antibiotics.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
- 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
- Dysregulated androgen synthesis and anti-androgen resistance in advanced prostate cancer.American journal of clinical and experimental urology · 2021Review
- Amide Bond Bioisosteres: Strategies, Synthesis, and Successes.Journal of medicinal chemistry · 2020Review
- Transcript Levels of Aldo-Keto Reductase Family 1 Subfamily C (AKR1C) Are Increased in Prostate Tissue of Patients with Type 2 Diabetes.Journal of personalized medicine · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAldo-keto reductase 1C3 [AKR1C3;17β-hydroxysteroid dehydrogenase type 5 (17βHSD5)], plays a crucial role in persistent production of androgens despite castration, by catalysing conversion of the adrenal androgens dehydroepiandrosterone and androstenedione (AD) into androstenediol and testosterone (T). Hence, AKR1C3 is a promising therapeutic target in castration-resistant prostate cancer, as combination of an AKR1C3 inhibitor and a gonadotropin-releasing hormone analogue may lead to complete androgen blockade. This study describes the preclinical characterisation of the novel AKR1C3 inhibitor ASP9521.
methodsThe inhibitory effect of ASP9521 on AKR1C3-mediated conversion from AD into T was evaluated both in vitro and in vivo, using CWR22R xenografted mice. The effect of ASP9521 on PSA production and cell proliferation was tested using LNCaP cells stably expressing human AKR1C3 (LNCaP-AKR1C3). Pharmacokinetics of ASP9521 were studied in rats, dogs and cynomolgus monkeys.
resultsASP9521 inhibited conversion of AD into T by recombinant human or cynomolgus monkey AKR1C3 in a concentration-dependent manner (IC50,human: 11 nmol/L; IC50,monkey: 49 nmol/L). ASP9521 showed >100-fold selectivity for AKR1C3 over the isoform AKR1C2. In LNCaP-AKR1C3 cells, ASP9521 suppressed AD-dependent PSA production and cell proliferation. In CWR22R xenografts, single oral administration of ASP9521 (3 mg/kg) inhibited AD-induced intratumoural T production and this inhibitory effect was maintained for 24 h. After oral administration, ASP9521 was rapidly eliminated from plasma, while its intratumoural concentration remained high. The bioavailability of ASP9521 after oral administration (1 mg/kg) was 35 %, 78 % and 58 % in rats, dogs and monkeys, respectively.
conclusionsASP9521 is a potent, selective, orally bioavailable AKR1C3 inhibitor.
Indexed as
Identifiers
What OpenQuestion holds
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.