ArticleScientific reports2020
A high throughput zebrafish chemical screen reveals ALK5 and non-canonical androgen signalling as modulators of the pkd2
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 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
14 citing papers in PubMed, 31 citations in OpenAlex.
- ift140 -Deficient Zebrafish as a Model for Kidney Cystogenesis and an F0-Based Screen for Genetic Modifiers of Kidney Cysts.Journal of the American Society of Nephrology : JASN · 2026Article
- Article
- Review
- Beyond drug discovery: Exploring the physiological and methodological dimensions of zebrafish in diabetes research.Experimental physiology · 2024Review
- (Zebra)fishing for nephrogenesis genes.Tissue barriers · 2024Review
- The role of cilia during organogenesis in zebrafish.Open biology · 2023Review
- Flight for fish in drug discovery: a review of zebrafish-based screening of molecules.Biology letters · 2023Review
- Prioritized polycystic kidney disease drug targets and repurposing candidates from pre-cystic and cystic mouse Pkd2 model gene expression reversion.Molecular medicine (Cambridge, Mass.) · 2023Article
- An assessment of vaping-induced inflammation and toxicity: A feasibility study using a 2-stage zebrafish and mouse platform.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2022Article
- Deep learning is widely applicable to phenotyping embryonic development and disease.Development (Cambridge, England) · 2021Article
- Aquatic models of human ciliary diseases.Genesis (New York, N.Y. : 2000) · 2021Review
- The Controversial Role of Fibrosis in Autosomal Dominant Polycystic Kidney Disease.International journal of molecular sciences · 2020Review
- An Overview of In Vivo and In Vitro Models for Autosomal Dominant Polycystic Kidney Disease: A Journey from 3D-Cysts to Mini-Pigs.International journal of molecular sciences · 2020Review
- Zebrafish for Personalized Regenerative Medicine; A More Predictive Humanized Model of Endocrine Disease.Frontiers in endocrinology · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic cause of end-stage renal failure in humans and results from germline mutations in PKD1 or PKD2. Despite the recent approval of tolvaptan, safer and more effective alternative drugs are clearly needed to slow disease progression. As a first step in drug discovery, we conducted an unbiased chemical screen on zebrafish pkd2 mutant embryos using two publicly available compound libraries (Spectrum, PKIS) totalling 2,367 compounds to identify novel treatments for ADPKD. Using dorsal tail curvature as the assay readout, three major chemical classes (steroids, coumarins, flavonoids) were identified from the Spectrum library as the most promising candidates to be tested on human PKD1 cystic cells. Amongst these were an androgen, 5α-androstane 3,17-dione, detected as the strongest enhancer of the pkd2 phenotype but whose effect was found to be independent of the canonical androgen receptor pathway. From the PKIS library, we identified several ALK5 kinase inhibitors as strong suppressors of the pkd2 tail phenotype and in vitro cyst expansion. In summary, our results identify ALK5 and non-canonical androgen receptors as potential therapeutic targets for further evaluation in drug development for ADPKD.
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.