ArticleCell cycle (Georgetown, Tex.)2012
CDK inhibitors R-roscovitine and S-CR8 effectively block renal and hepatic cystogenesis in an orthologous model of ADPKD.
Article in Cell cycle (Georgetown, Tex.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 64 citations in OpenAlex.
- Advances in the Treatment of Autosomal Dominant Polycystic Kidney Disease and Novel Therapeutic Targets.Current issues in molecular biology · 2026Review
- Epithelial Dynamics of Cystogenesis in Genetic Models of Autosomal Dominant Polycystic Kidney Disease.Cells · 2026Article
- Physiologic mechanisms underlying polycystic kidney disease.Physiological reviews · 2025Review
- A miRNA-Based Approach in Autosomal Dominant Polycystic Kidney Disease: Challenges and Insights from Adult to Pediatric Evidence.Molecular diagnosis & therapy · 2025Review
- Clinical findings, underlying pathogenetic processes and treatment of vascular dysfunction in autosomal dominant polycystic kidney disease.Renal failure · 2023Review
- The lonidamine derivative H2-gamendazole reduces cyst formation in polycystic kidney disease.American journal of physiology. Renal physiology · 2022Article
- Autosomal Dominant Polycystic Kidney Disease: From Pathophysiology of Cystogenesis to Advances in the Treatment.International journal of molecular sciences · 2022Review
- Therapeutic advances in ADPKD: the future awaits.Journal of nephrology · 2022Review
- Renal plasticity revealed through reversal of polycystic kidney disease in mice.Nature genetics · 2021Article
- Pharmacological Inhibition of Cyclin-Dependent Kinases Triggers Anti-Fibrotic Effects in Hepatic Stellate Cells In Vitro.International journal of molecular sciences · 2020Article
- Role of cyclin-dependent kinase 2 in the progression of mouse juvenile cystic kidney disease.Laboratory investigation; a journal of technical methods and pathology · 2020Article
- Apoptosis and autophagy in polycystic kidney disease (PKD).Cellular signalling · 2020Review
- Therapeutic perspectives for structural and functional abnormalities of cilia.Cellular and molecular life sciences : CMLS · 2019Review
- Casein kinase 1ε and 1α as novel players in polycystic kidney disease and mechanistic targets for (R)-roscovitine and (S)-CR8.American journal of physiology. Renal physiology · 2018Article
- Patient-iPSC-Derived Kidney Organoids Show Functional Validation of a Ciliopathic Renal Phenotype and Reveal Underlying Pathogenetic Mechanisms.American journal of human genetics · 2018Article
- A human patient-derived cellular model of Joubert syndrome reveals ciliary defects which can be rescued with targeted therapies.Human molecular genetics · 2017Article
- Article
- High-resolution genetic localization of a modifying locus affecting disease severity in the juvenile cystic kidneys (jck) mouse model of polycystic kidney disease.Mammalian genome : official journal of the International Mammalian Genome Society · 2016Article
- Reduction of ciliary length through pharmacologic or genetic inhibition of CDK5 attenuates polycystic kidney disease in a model of nephronophthisis.Human molecular genetics · 2016Article
- Nephronophthisis: should we target cysts or fibrosis?Pediatric nephrology (Berlin, Germany) · 2016Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Autosomal dominant polycystic kidney disease (ADPKD) and other forms of PKD are associated with dysregulated cell cycle and proliferation. Although no effective therapy for the treatment of PKD is currently available, possible mechanism-based approaches are beginning to emerge. A therapeutic intervention targeting aberrant cilia-cell cycle connection using CDK-inhibitor R-roscovitine showed effective arrest of PKD in jck and cpk models that are not orthologous to human ADPKD. To evaluate whether CDK inhibition approach will translate into efficacy in an orthologous model of ADPKD, we tested R-roscovitine and its derivative S-CR8 in a model with a conditionally inactivated Pkd1 gene (Pkd1 cKO). Similar to ADPKD, Pkd1 cKO mice developed renal and hepatic cysts. Treatment of Pkd1 cKO mice with R-roscovitine and its more potent and selective analog S-CR8 significantly reduced renal and hepatic cystogenesis and attenuated kidney function decline. Mechanism of action studies demonstrated effective blockade of cell cycle and proliferation and reduction of apoptosis. Together, these data validate CDK inhibition as a novel and effective approach for the treatment of ADPKD.
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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.