{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T22:04:37Z","timestamp":1790546677032,"version":"4.1.0"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2019,5,8]],"date-time":"2019-05-08T00:00:00Z","timestamp":1557273600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003958","name":"Dutch Technology Foundation","doi-asserted-by":"publisher","award":["11823"],"award-info":[{"award-number":["11823"]}],"id":[{"id":"10.13039\/501100003958","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Netherlands Organization for Scientific Research"},{"DOI":"10.13039\/501100003958","name":"Dutch Technology Foundation","doi-asserted-by":"publisher","award":["14410"],"award-info":[{"award-number":["14410"]}],"id":[{"id":"10.13039\/501100003958","id-type":"DOI","asserted-by":"publisher"}]},{"name":"EU-FP7\u2014Systems Microscopy NoE","award":["258068"],"award-info":[{"award-number":["258068"]}]},{"DOI":"10.13039\/501100002997","name":"Dutch Kidney Foundation","doi-asserted-by":"publisher","award":["4OIP12"],"award-info":[{"award-number":["4OIP12"]}],"id":[{"id":"10.13039\/501100002997","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Polycystic kidney disease (PKD) is a prevalent genetic disorder, characterized by the formation of kidney cysts that progressively lead to kidney failure. The currently available drug tolvaptan is not well tolerated by all patients and there remains a strong need for alternative treatments. The signaling rewiring in PKD that drives cyst formation is highly complex and not fully understood. As a consequence, the effects of drugs are sometimes difficult to predict. We previously established a high throughput microscopy phenotypic screening method for quantitative assessment of renal cyst growth. Here, we applied this 3D cyst growth phenotypic assay and screened 2320 small drug-like molecules, including approved drugs. We identified 81 active molecules that inhibit cyst growth. Multi-parametric phenotypic profiling of the effects on 3D cultured cysts discriminated molecules that showed preferred pharmacological effects above genuine toxicological properties. Celastrol, a triterpenoid from Tripterygium Wilfordii, was identified as a potent inhibitor of cyst growth in vitro. In an in vivo iKspCre-Pkd1lox,lox mouse model for PKD, celastrol inhibited the growth of renal cysts and maintained kidney function.<\/jats:p>","DOI":"10.1093\/jmcb\/mjz029","type":"journal-article","created":{"date-parts":[[2019,4,26]],"date-time":"2019-04-26T11:27:26Z","timestamp":1556278046000},"page":"644-653","source":"Crossref","is-referenced-by-count":11,"title":["In vitro 3D phenotypic drug screen identifies celastrol as an effective<i>in vivo<\/i>inhibitor of polycystic kidney disease"],"prefix":"10.1093","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7478-4704","authenticated-orcid":false,"given":"Tijmen H","family":"Booij","sequence":"first","affiliation":[{"name":"Division of Toxicology, Leiden Academic Centre for Drug Research (LACDR), Leiden University, Leiden, The Netherlands"},{"name":"NEXUS Personalized Health Technologies, ETH Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wouter N","family":"Leonhard","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Leiden University Medical Center (LUMC), Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hester","family":"Bange","sequence":"additional","affiliation":[{"name":"OcellO B.V., Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuan","family":"Yan","sequence":"additional","affiliation":[{"name":"OcellO B.V., Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiel","family":"Fokkelman","sequence":"additional","affiliation":[{"name":"Division of Toxicology, Leiden Academic Centre for Drug Research (LACDR), Leiden University, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna J","family":"Plugge","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Leiden University Medical Center (LUMC), Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberley A M","family":"Veraar","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Leiden University Medical Center (LUMC), Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes G","family":"Dauwerse","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Leiden University Medical Center (LUMC), Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard J P","family":"van Westen","sequence":"additional","affiliation":[{"name":"Division of Medicinal Chemistry, Leiden Academic Centre for Drug Research (LACDR), Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bob","family":"van de Water","sequence":"additional","affiliation":[{"name":"Division of Toxicology, Leiden Academic Centre for Drug Research (LACDR), Leiden University, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo S","family":"Price","sequence":"additional","affiliation":[{"name":"Division of Toxicology, Leiden Academic Centre for Drug Research (LACDR), Leiden University, Leiden, The Netherlands"},{"name":"OcellO B.V., Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorien J M","family":"Peters","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Leiden University Medical Center (LUMC), Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,5,8]]},"reference":[{"key":"2021020111445313600_ref1","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1042\/bj20021619","article-title":"Curcumin activates the haem oxygenase-1 gene via regulation of Nrf2 and the antioxidant-responsive element","volume":"371","author":"Balogun","year":"2003","journal-title":"Biochem. 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