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-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.
Obligado
S H
SH
Division of Nephrology, New York University School of Medicine, New York, New York 10016, USA.
Ibraghimov-Beskrovnaya
O
O
Zuk
A
A
Meijer
L
L
Nelson
P J
PJ
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors*; D006801:Humans; D007674:Kidney Diseases / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use
D015415:Biomarkers; D047428:Protein Kinase Inhibitors; D018844:Cyclin-Dependent Kinases; D038362:Glycogen Synthase Kinase 3