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1篇 您的检索式：作者名="Wouter N.Leonhard"

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		题名	作者	年代	出处	被引量
	1	In vitro 3D phenotypic drug screen identifies celastrol as an effective in vivo inhibitor of polycystic kidney disease显示文摘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 signalling 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-Pkd1^lox,lox mouse model for PKD,celastrol inhibited the growth of renal cysts and maintained kidney function.	Tijmen H.Booij Wouter N.Leonhard Hester Bange Kuan Yan Michiel Fokkelman Anna J.Plugge Kimberley A.M.Veraar Johannes G.Dauwerse Gerard J.P.van Westen Bob van de Water Leo S.Price Dorien j.M.Peters	2020	Journal of Molecular Cell Biology2020，12，8：	1

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