CDK/GSK-3 inhibitors as therapeutic agents for parenchymal renal diseases

Drug discovery to lessen the burden of chronic renal failure and end-stage renal disease remains a principle goal of translational research in nephrology. In this review, we provide an overview of the current development of small molecule cyclin-dependent kinase (CDK)/glycogen synthase kinase-3 (GSK...

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Bibliographic Details
Published in:	Kidney international Vol. 73; no. 6; pp. 684 - 690
Main Authors:	Obligado, S.H., Ibraghimov-Beskrovnaya, O., Zuk, A., Meijer, L., Nelson, P.J.
Format:	Journal Article
Language:	English
Published:	New York, NY Elsevier Inc 01-03-2008 Nature Publishing Elsevier Limited Nature Publishing Group
Subjects:	Animals apoptosis Biochemistry, Molecular Biology Biological and medical sciences Biological Markers Biomarkers - metabolism chronic kidney disease Cyclin-Dependent Kinases Cyclin-Dependent Kinases - antagonists & inhibitors end-stage renal disease Glycogen Synthase Kinase 3 Glycogen Synthase Kinase 3 - antagonists & inhibitors Humans immunology Kidney Diseases Kidney Diseases - drug therapy Kidney Diseases - metabolism Kidneys Life Sciences Medical sciences Mice Nephrology. Urinary tract diseases Nephropathies. Renovascular diseases. Renal failure proliferation Protein Kinase Inhibitors Protein Kinase Inhibitors - pharmacology Protein Kinase Inhibitors - therapeutic use Renal failure Urinary system involvement in other diseases. Miscellaneous apoptosis chronic kidney disease proliferation end-stage renal disease immunology Cell proliferation Kidney disease Nephrology Urinary system disease Parenchyma Terminal stage Chronic kidney disease Urology Cyclin dependent kinase inhibitor Immunology Treatment Cell death Renal failure Apoptosis
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Summary:	Drug discovery to lessen the burden of chronic renal failure and end-stage renal disease remains a principle goal of translational research in nephrology. In this review, we provide an overview of the current development of small molecule cyclin-dependent kinase (CDK)/glycogen synthase kinase-3 (GSK-3) inhibitors as therapeutic agents for parenchymal renal diseases. The emergence of this drug family has resulted from the recognition that CDKs and GSK-3s play critical roles in the progression and regression of many kidney diseases. CDK/GSK-3 inhibitors suppress pathogenic proliferation, apoptosis, and inflammation, and promote regeneration of injured tissue. Preclinical efficacy has now been demonstrated in mesangial proliferative glomerulonephritis, crescentic glomerulonephritis, collapsing glomerulopathy, proliferative lupus nephritis, polycystic kidney diseases, diabetic nephropathy, and several forms of acute kidney injury. Novel biomarkers of therapy are aiding the process of drug development. This review will highlight these advancements in renal therapeutics.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-3 content type line 23 ObjectType-Review-1
ISSN:	0085-2538 1523-1755
DOI:	10.1038/sj.ki.5002731