ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2018
Ganetespib limits ciliation and cystogenesis in autosomal-dominant polycystic kidney disease (ADPKD).
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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The trial behind it
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Who cites it
21 citing papers in PubMed, 36 citations in OpenAlex.
- Pathogenic Pathways and Therapeutic Strategies in Autosomal Dominant Polycystic Kidney Disease (ADPKD).Journal of cellular signaling · 2025Article
- Inhibition of asparagine synthetase effectively retards polycystic kidney disease progression.EMBO molecular medicine · 2024Article
- Racgap1 knockdown results in cells with multiple cilia due to cytokinesis failure.Annals of human genetics · 2024Article
- Loss of Pkd1 limits susceptibility to colitis and colorectal cancer.Oncogenesis · 2023Article
- Role of Ganetespib, an HSP90 Inhibitor, in Cancer Therapy: From Molecular Mechanisms to Clinical Practice.International journal of molecular sciences · 2023Review
- The role of primary cilia in thyroid diseases.Frontiers in endocrinology · 2023Review
- Patterns of Ciliation and Ciliary Signaling in Cancer.Reviews of physiology, biochemistry and pharmacology · 2023Review
- The lonidamine derivative H2-gamendazole reduces cyst formation in polycystic kidney disease.American journal of physiology. Renal physiology · 2022Article
- Review
- Review
- Polycystin-1 dependent regulation of polycystin-2 via GRP94, a member of HSP90 family that resides in the endoplasmic reticulum.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Characterization of Primary Cilia in Osteoblasts Isolated From Patients With ADPKD and CKD.JBMR plus · 2021Article
- The Role of Primary Cilia in Thyroid Cancer: From Basic Research to Clinical Applications.Frontiers in endocrinology · 2021Review
- Insights Into the Molecular Mechanisms of Polycystic Kidney Diseases.Frontiers in physiology · 2021Review
- Loss of Cilia Does Not Slow Liver Disease Progression in Mouse Models of Autosomal Recessive Polycystic Kidney Disease.Kidney360 · 2020Article
- Loss of polycystins suppresses deciliation via the activation of the centrosomal integrity pathway.Life science alliance · 2020Article
- ADPKD current management and ongoing trials.Journal of nephrology · 2020Review
- Informatics-guided drug repurposing for Autosomal Dominant Polycystic Kidney Disease (ADPKD).EBioMedicine · 2020Article
- Unexpected Activities in Regulating Ciliation Contribute to Off-target Effects of Targeted Drugs.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Microscopy-Based Automated Live Cell Screening for Small Molecules That Affect Ciliation.Frontiers in genetics · 2019Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Autosomal-dominant polycystic kidney disease (ADPKD) is associated with progressive formation of renal cysts, kidney enlargement, hypertension, and typically end-stage renal disease. In ADPKD, inherited mutations disrupt function of the polycystins (encoded by PKD1 and PKD2), thus causing loss of a cyst-repressive signal emanating from the renal cilium. Genetic studies have suggested ciliary maintenance is essential for ADPKD pathogenesis. Heat shock protein 90 (HSP90) clients include multiple proteins linked to ciliary maintenance. We determined that ganetespib, a clinical HSP90 inhibitor, inhibited proteasomal repression of NEK8 and the Aurora-A activator trichoplein, rapidly activating Aurora-A kinase and causing ciliary loss in vitro. Using conditional mouse models for ADPKD, we performed long-term (10 or 50 wk) dosing experiments that demonstrated HSP90 inhibition caused durable in vivo loss of cilia, controlled cystic growth, and ameliorated symptoms induced by loss of Pkd1 or Pkd2. Ganetespib efficacy was not increased by combination with 2-deoxy-d-glucose, a glycolysis inhibitor showing some promise for ADPKD. These studies identify a new biologic activity for HSP90 and support a cilia-based mechanism for cyst repression.-Nikonova, A. S., Deneka, A. Y., Kiseleva, A. A., Korobeynikov, V., Gaponova, A., Serebriiskii, I. G., Kopp, M. C., Hensley, H. H., Seeger-Nukpezah, T. N., Somlo, S., Proia, D. A., Golemis, E. A. Ganetespib limits ciliation and cystogenesis in autosomal-dominant polycystic kidney disease (ADPKD).
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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.