Ruboxistaurin, a protein kinase C beta inhibitor, as an emerging treatment for diabetes microvascular complications.
OBJECTIVE
To review current clinical data regarding the pharmacologic actions of ruboxistaurin (LY333531) mesylate, an inhibitor of protein kinase C (PKC) beta, and its role to potentially reduce the development and/or the progression of diabetic microvascular complications.


METHODS
Primary literature was obtained via a MEDLINE search (1966-August 2004) and through review of pertinent abstracts and presentations at major medical meetings.


METHODS
Literature relevant to PKC physiology, the pharmacokinetics of ruboxistaurin, and data evaluating the use of ruboxistaurin in treating diabetic microvascular complications in human and relevant animal models was reviewed.


RESULTS
PKC is part of a group of intracellular signaling molecules activated in response to various specific hormonal, neuronal, and growth factor stimuli. Hyperglycemia leads to PKC beta 1 and 2 isoform activation, which experimentally has been shown to contribute to the development and progression of diabetic microvascular complications (retinopathy, nephropathy, neuropathy) through various biochemical mechanisms. Animal and/or human studies using ruboxistaurin mesylate, a novel, highly selective inhibitor of PKC beta, have shown delay in the progression and, in some cases, reversal of diabetic retinopathy, nephropathy, and neuropathy.


CONCLUSIONS
Ruboxistaurin mesylate, by inhibiting excessive activation of certain PKC isoforms, has the potential to reduce the burden of microvascular complications for patients with diabetes.
Joy
Scott V
SV
Department of Medicine, Duke University Medical Center, Durham, NC 27705-0493, USA.
Scates
Ann C
AC
Bearelly
Srilaxmi
S
Dar
Moahad
M
Taulien
Christina A
CA
Goebel
Jason A
JA
Cooney
Michael J
MJ
D000818:Animals; D002986:Clinical Trials as Topic; D003925:Diabetic Angiopathies / Q000188:drug therapy* / Q000201:enzymology; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000201:enzymology; D003929:Diabetic Neuropathies / Q000188:drug therapy / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016239:MEDLINE; D008301:Maleimides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D064546:Protein Kinase C beta; D016896:Treatment Outcome
D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; C099154:ruboxistaurin; D011493:Protein Kinase C; D064546:Protein Kinase C beta