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.