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

Kidney Int. 2008 Mar;73(6):684-90. doi: 10.1038/sj.ki.5002731. Epub 2007 Dec 19.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Cyclin-Dependent Kinases / antagonists & inhibitors*
  • Glycogen Synthase Kinase 3 / antagonists & inhibitors*
  • Humans
  • Kidney Diseases / drug therapy*
  • Kidney Diseases / metabolism
  • Mice
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Kinase Inhibitors / therapeutic use

Substances

  • Biomarkers
  • Protein Kinase Inhibitors
  • Cyclin-Dependent Kinases
  • Glycogen Synthase Kinase 3